Prevention / treatment of Hyper-inflammation / Cytokine Storm
Up to 23 sites
Including MD Anderson and other ZUMA-1 sites
Break CAR-T Efficacy/Toxicity Linkage
Prophylaxis as sequenced therapy with Yescarta in r/r DLBCL
Chronic myelomonocytic leukemia (CMML)
Lenzilumab + azacitidine in NRAS, KRAS or CBL mutant-positive newly-diagnosed patients
Prevention/Treatment of Acute GvHD
Up to 40 sites
Active, almost fully recruited
1 Phase III may not be necessary for approval in ZUMA-19; precedent is CAR-Ts to date have been approved on Phase II data
Published scientific evidence links GM-CSF expression to serious and potentially life-threatening outcomes in respiratory conditions such as COVID-19 pneumonia. Evidence also indicates a potential role of GM-CSF expression in serious and potentially life-threatening side-effects associated with CAR-T therapy, and reduced efficacy in CAR-T therapies approved by the US Food and Drug Administration (“FDA”). As a result, while we believe our leadership position in GM-CSF pathway science and cytokine storm presents us with a diverse set of development opportunities, we currently are focused on developing lenzilumab for three primary indications:
As a therapy treating severe and critical hospitalized patients with confirmed COVID-19 pneumonia, which is the majority of hospitalized patients who are hypoxic and not yet on invasive mechanical ventilation (“IMV”);
As a prophylactic therapy ahead of CAR-T administration in CD19 targeted CAR-T therapies; and
As an early treatment or potential prophylaxis for acute GvHD following HSCT in high and intermediate risk patients.
In addition to these programs with lenzilumab, we are also exploring the effectiveness of our GM-CSF neutralization technologies (either through the use of lenzilumab as a neutralizing antibody, or through GM-CSF gene knockout) in combination with other CAR-T, T-cell engaging, and immunotherapy treatments to break the efficacy/toxicity linkage.
Our clinical-stage pipeline also comprises a further Phase I study with ifabotuzumab (“ifab”) in glioblastoma multiforme (“GBM”). The GBM study is nearly fully enrolled. We believe ifab may have potential in other solid cancers. We also have a focus on creating safer and more effective CAR-T therapies in hematologic malignancies and solid tumors via three key modalities:
Combining FDA-approved and development stage CAR-T therapies with lenzilumab;
Creating next-generation gene-edited CAR-T therapies using GM-CSF gene knockout technologies; and
Exploring the effectiveness of our GM-CSF neutralization technologies (either through the use of lenzilumab as a neutralizing antibody or through GM-CSF gene knockout) in combination with other CAR-T, T-cell engaging, and immunotherapy treatments, including allogeneic HSCT.
These product candidates are in the early stage of development and will require substantial time, resources, research and development, and regulatory approval prior to commercialization. Furthermore, none of these product candidates have been approved for marketing and it may be years, if this occurs at all.
We believe that we have built an intellectual property position in the area of GM-CSF neutralization through multiple approaches and mechanisms, as they pertain to COVID-19, CAR-T, GvHD and multiple other oncology/transplantation, inflammation, fibrosis and autoimmune conditions which may be driven by GM-CSF.