LENZILUMAB™ OVERVIEW LENZILUMAB IN COVID-19 Lenzilumab, Humanigen’s lead product candidate, is a late clinical- 2020 DEVELOPMENT TIMELINE stage monoclonal antibody developed with Humaneered® March — Cytokine storm identified in COVID-19 patients technology designed to optimize antibody properties. — HGEN expands lenzilumab clinical focus to include • Shown to neutralize immune signaling ability of granulocyte- COVID-19 based on mechanism of action macrophage colony-stimulating factor (GM-CSF), a key — FDA approves Emergency IND of lenzilumab for cytokine responsible for the initiation of the inflammatory compassionate use cascade and immune hyper-response known as cytokine storm April — Treatment of patients begins at Mayo Clinic under • Currently being evaluated to prevent/treat cytokine storm compassionate use in patients with a range of conditions, including patients — FDA approves initiation of lenzilumab undergoing CAR-T therapy and patients hospitalized with Phase 3 study COVID-19 May — First patient dosed in lenzilumab Phase 3 study POTENTIAL IN TREATING COVID-19 June — Positive data announced from patients treated at Mayo Clinic under compassionate use Several studies suggest that cytokine storm and elevated levels of GM-CSF are correlated with the worst clinical outcomes in COVID-19 — Additional positive analysis announced of pneumonia, including acute respiratory distress syndrome, lung injury, lenzilumab versus remdesivir multi-organ failure and death. July — HGEN expands partnership with Catalent Biologics to ramp up manufacturing of lenzilumab The ability of lenzilumab to neutralize the cytokine GM-CSF, which is key in the initiation of cytokine storm, has been shown to improve the — NIH selects lenzilumab for relative likelihood of survival without need for invasive mechanical ACTIV-5/Big Effect Trial August ventilation, time to recovery and need for intensive care (ICU) in — Lenzilumab Phase 3 trial expanded to Brazil patients with COVID-19. — Lenzilumab demonstrates positive results in a Key studies include: case-control study published by Mayo Clinic September • Positive results from a global Phase 3 registration study of — DSMB recommends Phase 3 trial to continue lenzilumab in 520 hospitalized COVID-19 patients (NCT0435152) without modification
• NIH-sponsored ACTIV-5/Big Effect Trial (BET) which will — HGEN partners with Lonza and Thermo Fisher for lenzilumab manufacturing evaluate lenzilumab in combination with remdesivir in October hospitalized patients with COVID-19 — First patient dosed in NIH ACTIV-5/Big Effect Trial November • Positive results from a multi-center case-cohort study published — HGEN announces CRADA with US government to by Mayo Clinic in patients hospitalized with COVID-19 pneumonia develop lenzilumab Having previously published data demonstrating the ability of — Encouraging interim analysis supports the potential for lenzilumab to prevent and/or treat cytokine storm, lenzilumab has lenzilumab over and above current standard of care the potential to be used as a monotherapy or in combination with a 2021 direct- acting antiviral, like remdesivir, in COVID-19, given the differing January — HGEN partners with EVERSANA to support launch and commercialization of lenzilumab mechanisms of action. — HGEN announces addition of BARDA and Expansion of CRADA with US government
— HGEN announces CDMO with Emergent Humanigen aims to advance BioSolutions, expands agreement with Ajinomoto lenzilumab through the — HGEN completes enrollment in lenzilumab regulatory pathway for potential Phase 3 study February — HGEN announces cGMP Manufacturing Agreement with Avid Bioservices Emergency Use Authorization in Q2 2021. March — Humanigen expands anti-GM-CSF Patent Portfolio — Humanigen reports positive Phase 3 topline results
Lenzilumab For more information, contact Grace Catlett: [email protected] Fact Sheet ADDITIONAL INDICATIONS Additional trials are underway to evaluate the potential of lenzilumab in other settings, including:
• Potential to improve efficacy of CAR-T therapies while • Early intervention in adults at high risk for acute graft versus simultaneously preventing cytokine storm (also referred to as host disease (GvHD) after allogeneic hematopoietic stem cell cytokine release syndrome, or CRS) and reducing associated transplantation (HSCT) in partnership with IMPACT Clinical neurologic toxicities and other serious, potentially life- Trials (UK) threatening effects • Treatment of refractory chronic myelomonocytic leukemia • The ZUMA-19 pivotal study, conducted in collaboration with (CMML) patients with RAS pathway mutations Kite Pharma, a Gilead Company, is a trial of sequenced • Evaluating lenzilumab plus azacitidine in newly-diagnosed therapy of lenzilumab with Yescarta (axicabtagene ciloleucel) CMML patients who express NRAS/KRAS/CBL mutations in adults with relapsed/refractory diffuse large B-cell (Australia) lymphoma DLBCL designed to investigate if lenzilumab can break the efficacy/toxicity link associated with CAR-T therapy.)
LENZILUMAB CLINICAL-STAGE PIPELINE
Indication Phase 1 Phase 2 Phase 3
Prevention/treatment of Fully Enrolled COVID-19 cytokine storm 520 patients in partnership with Mayo Clinic Positive data reported
Prevention/treatment of Recruiting COVID-19 cytokine storm 200 patients NIAID/DMID sponsored
ZUMA-19* Prophylaxis as sequenced Break CAR-T Efficacy/ therapy with Yescarta in r/r Recruiting Toxicity Linkage DLBCL
Prevention/Treatment of Allogeneic HSCT Advanced planning Acute GvHD
Lenzilumab + azacitidine in NRAS, Chronic myelomonocytic KRAS or CBL mutant-positive Advanced planning leukemia (CMML) newly-diagnosed patients
*Phase III may not be necessary for approval in ZUMA-19; precedent is CAR-Ts to date have been approved on Phase II data
SAFETY PROFILE Lenzilumab has been shown to be safe in clinical settings following administration to 375 patients in multiple indications, including severe respiratory conditions and leukemia, with no serious or adverse events attributable to lenzilumab.
Humanigen has developed a neutralizing, IgG1, monoclonal antibody against human GM-CSF, using proprietary Humaneered® technology.
Lenzilumab For more information, contact Grace Catlett: [email protected] Fact Sheet