GEn1E compounds are parallel signal modulators. They have a unique MOA with dual modulation where they inhibit the inflammatory MK2 pathway, and spare the anti-inflammatory MSK1/2 pathway.

From discovery to Phase 2 in ~2.5 years with seed capital

FDA approved Phase 2 study enrolling ARDS patients
Received Fast Track designation from FDA
Partnership with BARDA and Vituity
Completed Phase 1 SAD/MAD study in 48 humans
Pre-IND to FDA for 2nd indication completed
IV for Acute
In addition,
2nd drug for Chronic Oral is progressing rapidly
3rd drug (using 2nd target ERK) is optimized
Patent portfolio is robust and expanding
21+ Novel, Dual Signal Modulators developed
Oral for Chronic
Our Solution

1. Discovery of a new Binding Pocket

Traditional kinase inhibitors focus on the ATP binding pocket with covalent bonding. Our platform allows us to identify new binding pockets where we can target specific functions using allosteric binding.

2. A unique and validated MOA (presented at ATS '23)

GEn1E’s novel compounds bind to a unique binding site. Unlike previous generation compounds which are non-selective and immunosuppressive due to their inhibitor characteristics, GEn1E’s selective & dual signal modifiers use a differentiated Mechanism of Action for treating inflammation.
Resting state
In resting state, p38⍺ resides in the cytoplasm and MK2 is in the nucleus.
p38⍺ transports to nucleus with stress response
Activated p38⍺ translocates to the nucleus and phosphorylates intranuclear substrates including MK2 and anti-inflammatory substrates like MSK1/2.
With no drug
Phosphorylated MK2 chaperones p38⍺ from the nucleus to the cytoplasm. Intranuclear p38⍺ signaling is truncated. MK2 (complexed with p38⍺) phosphorylates Hsp27 (endothelial leak, leukocyte recruitment) and RNA binding proteins (cytokine expression).
With GEn-1124
GEn-1124 binds to unique binding site on p38⍺ destabilizing p38⍺:MK2 binding so MK2 exits the nucleus without p38⍺. In the absence of cytoplasmic p38⍺, MK2 is more quickly dephosphorylated/inactivated. As a result, this reduces pro-inflammatory cytokine expression (post-transcriptional). This also decreases Hsp27 phosphorylation, thereby stabilizing the endothelial barrier. Intranuclear p38⍺ signaling persists including anti-inflammatory substrates (MSK1/2, CREB).

Phase 1 SAD/MAD study completed

The study was successful with favorable Safety & PK/PD results unlike previous gen drugs which had significant side effects
Side Effects
Previous gen p38s
Secondary Infections
Elevated ALT/AST
Elevated Creatine Kinase
Severe Rash
Severe Dizziness
Unpredicatable Human PK/PD

Proteomics Data

Proteins, the study of which are important for understanding a range of biological conditions, including inflammation, cell regulation, immune responses, and oncology, are not as amenable to analysis. Most technologies for proteomics have lagged in terms of throughput, specificity, and cost. Our partner, Olink Proteomics has bridged this gap.

Our partnership with Olink Proteomics which utilizes the strengths of PCR and NGS (next generation sequencing) to establish a multiplex and high-throughput approach enabled us to measuring thousands of proteins in a small sample and produced the following results from our Phase 1 study.
Pro-Inflammatory (all down)
Target Vascular Leak (all down)
Anti-Inflammatory (no change)
Endothelial Stabilization
Reduced Apoptosis/Necrosis
Reduced Fibrosis (all down)
Epithelial Dysfunction