Chimerix Inc. is focused on developing innovative therapies to combat deadly diseases, particularly through its lead drug candidate, ONC201 (dordaviprone). This first-in-class small molecule is designed to selectively bind to the G-protein coupled dopamine receptor D2 (DRD2) and the mitochondrial protease ClpP, showcasing its potential in treating advanced cancers, specifically those with the H3 K27M mutation found in gliomas. The ongoing Phase 3 ACTION study aims to evaluate the efficacy of ONC201 in newly diagnosed patients with H3 K27M-mutant diffuse glioma following radiotherapy, highlighting the company's commitment to addressing unmet medical needs in oncology.

In addition to its primary focus on H3 K27M-mutant gliomas, Chimerix is exploring the broader therapeutic potential of ONC201 in various advanced cancers. Preclinical studies have indicated promising results for ONC201 as a monotherapy or in combination with other treatments for conditions such as neuroendocrine cancers, including paraganglioma and pheochromocytoma. The company is actively conducting clinical trials to assess the drug's effectiveness and safety, with a strong emphasis on improving patient outcomes and survival rates in challenging cancer types.

United States

At Chimerix, we are on a mission to develop medicines that meaningfully improve and extend the lives of patients facing deadly diseases. With a focus in oncology, we are devoted to filling gaps in the treatment paradigm.

Cancer

Infectious Diseases

Chimerix Inc. 

Smallpox

TEMBEXA (brincidofovir)

Brain tumor

Glioma

ONC201 is the founding member of the imipridone class of anti-cancer small molecules which selectively targets Dopamine Receptor D2 (DRD2) and ClpP. ONC201-mediated cell death occurs via induction of the integrated stress response and upregulation of apoptotic factors, such as tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). It is dosed orally and has been well-tolerated and shown clinical activity in Phase I and II trials for specific advanced cancers.

Dordaviprone (ONC201)

Glioblastoma

Solid tumor/s

ONC206 is a DRD2 antagonist and ClpP agonist with nanomolar potency that demonstrates enhanced non-competitive DRD2 antagonism relative to ONC201 and disruption of DRD2 homodimers. ONC206 exhibits a distinct gene expression profile as well as single agent and combinatorial efficacy with ONC201 in cells with acquired resistance to ONC201. ONC206 is effective in preclinical models of difficult-to-treat neuroendocrine tumors and high-grade gliomas. It affects some of the same downstream pathways as ONC201, including activation of the integrated stress response and inhibition of Ras signaling, leading to selective killing of tumor cells.

ONC206

COVID-19

Infectious disease

DSTAT is a potential first-in-class glycosaminoglycan compound derived from porcine heparin that, compared to commercially available forms of heparin, may be dosed at higher levels without associated bleeding-related complications.
 
In vivo disease models have demonstrated that DSTAT can reduce HMGB1 in lung fluid, decrease immune cell infiltration in lungs and improve survival.&nbsp; &nbsp;Molecular drivers of these effects likely include DSTAT inhibition of HMGB1 binding to RAGE, inhibition of leukocyte lung infiltration via decreases in MCP-1 expression, and direct blocking of the cell adhesion molecule P-selectin.
 
HMGB1 and PF4 are proteins that can induce formation of NETS and regulate NET degradation; both are significantly elevated in COVID-19 patients and both are inhibited by binding to DSTAT.&nbsp; &nbsp;DSTAT inhibition of these two proteins may reduce formation of NETs and promote their clearance, thereby potentially preventing and treating coagulation disorders.
 
DSTAT inhibits several apparently key molecular drivers of COVID-19 pathology, including HMGB1, PF4 and P-selectin.&nbsp;DSTAT may effectively reduce excessive inflammation and coagulation disorders observed in COVID-19 via multiple mechanisms without the risk of severe bleeding events presented by fully anticoagulant forms of heparin.

Dociparstat sodium (DSTAT)

Acute myeloid leukemia

DSTATs mechanism of action is intended to enhance patient benefit when &nbsp;combined with an active agent, so to observe these results in &nbsp;HMA-refractory patients is promising
Dociparstat sodium is a potential first-in-class glycosaminoglycan &nbsp;compound derived from porcine heparin that has low anticoagulant &nbsp;activity. In vitro and in vivo animal model data support DSTAT’s &nbsp;potential to reduce the inflammation and cellular infiltration &nbsp;associated with acute lung injury and address coagulation disorders &nbsp;associated with COVID-19 pathology (HMGB1 and PF4). Separately, DSTAT &nbsp;inhibits the activities of several key proteins implicated in the &nbsp;viability of AML blasts and leukemic stem cells in the bone marrow &nbsp;during chemotherapy (e.g., CXCL12, selectins, HMGB1, elastase).&nbsp;&nbsp; &nbsp;Randomized AML Phase 2 data suggest that DSTAT may also accelerate &nbsp;platelet recovery post-chemotherapy via inhibition of PF4, a negative &nbsp;regulator of platelet production that impairs platelet recovery &nbsp;following chemotherapy.
<a href="https://ir.chimerix.com/news-releases/news-release-details/chimerix-reports-first-quarter-2020-financial-results-and">Source</a>

Chimerix Inc.

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