Humanigen showing positive interim Phase 3 results for lenzilumab to treat patients hospitalized with COVID-19

• The company's key drug candidate is lenzilumab, a recombinant monoclonal antibody • Conducting a Phase 3 clinical trial for lenzilumab to treat patients hospitalized with COVID-19  • Raised approximately $72.7 million in a Nasdaq public offering and uplisting in September 2020 What Humaningen’s does? Humanigen Inc (NASDAQ:HGEN) is in the early stages of work on a drug designed to reduce the sometimes dangerous side effects associated with a cancer therapy involving altered T cells. A goal is to improve the safety of so-called CAR-T therapies, used in the treatment of children with acute lymphoblastic leukemia and adults with advanced lymphomas. A frequent side-effect is cytokine release syndrome, which can include fever, nausea, headache, rash, rapid heartbeat, low blood pressure and trouble breathing. Reactions are often mild but occasionally life-threatening. The key drug candidate for the Burlingame, California, company is lenzilumab, a recombinant monoclonal antibody that neutralizes a substance that promotes growth of white blood cells but is also tied to inflammations that can occur during CAR-T therapies and lead to side effects. Pre-clinical work involving mice shows lenzilumab is effective in preventing the side effects and may make the CAR-T therapies more effective, according to Humanigen. The company has completed a Phase 1 clinical trial of patients with a type of leukemia conducted to identify the recommended Phase 2 dose of lenzilumab and to assess its safety. The company is planning on starting pivotal studies this year involving CAR-T and hopes to complete them by the end of 2020. Humanigen is also looking at two other drug candidates: ifabotuzumab and HGEN005. Ifabotuzumab, according to Humanigen, shows potential in attacking tumors by killing the stromal cells that protect them and the vasculature that feeds them without killing normal cells. The company says the first patients have been dosed in a Phase 1 trial at the Olivia Newton-John Cancer Research Institute in Australia to assess safety. The company’s other drug candidate, HGEN005, shows promise as a treatment for eosinophilia, a condition in which the number of eosinophil white blood cells is greatly increased. It can be a sign of a parasitic infection, an allergic reaction or cancer. Humanigen is talking with a leading US cancer center about pre-clinical testing in eosinophilic leukemia. Humanigen has also initiated a Phase 3 clinical trial to evaluate its antiGM-CSF antibody lenzilumab combined with remdesivir vs. remdesivir alone in COVID-19 patients.   How is it doing:   Under Cameron Durrant, a medical doctor and MBA who assumed the role of CEO in March 2016, the company has concentrated on realizing the promise of lenzilumab. Prior work for the turnaround specialist includes serving as CEO at three specialty pharma companies and senior executive roles at Pharmacia Corp, now part of Pfizer Inc (NYSE:PFE), as well Johnson & Johnson (NYSE: JNJ). Humanigen recently announced positive interim Phase 3 data on lenzilumab to treat patients hospitalized with COVID-19.  In a statement, the company said this interim analysis for sizing and powering, suggests that lenzilumab had a clinically meaningful impact on patient recovery, with an estimated 37% more recoveries observed in the lenzilumab arm of the randomized, placebo-controlled, double-blinded study versus current standard of care (SOC).  Humanigen said the data safety monitoring board (DSMB) composed of independent subject matter experts conducted an interim analysis of the unblinded data for trial sizing and powering and recommended increasing the target number of events (recoveries) from 257 to 402 to maintain the power of the study at 90%.  At the recommendation of the DSMB, the company said it plans to increase enrollment to achieve 402 events (about 515 patients). This increase in enrollment ensures an even higher probability of success in meeting the primary endpoint and maintains the power of the study at 90%. The next interim analysis for efficacy is planned when the study reaches 75% events (302 events), which will require about 390 patients to be enrolled in the trial. The company also signed a licensing deal for lenzilumab in South Korea and the Philippines worth as much as $20 million, including $6 million in an upfront payment when the agreement is executed. Inflection points: Next interim analysis for lenzilumab efficacy in its COVID-19 treatment trial  Filing for EUA in the first quarter of 2021 What the broker says: Following the release of Humanigen’s 3Q 2020 financial results (cash at the end of the quarter was $92 million), Roth Capital wrote the focus remains on the Phase 3 trial for anti-GM-CSF antibody lenzilumab in patients hospitalized with moderate-to-severe pneumonia arising from COVID-19. “While Humanigen remains blinded to the data, based on an interim analysis, the trial was recently upsized from 300 to 515 patients to maintain 90% power based on recommendations from the data safety monitoring committee. Based upon the adaptive trial design, an analysis by the data safety and monitoring board noted that the interim efficacy data was in what was termed the ‘promising zone’, and therefore per-protocol upsizing of the trial was allowed. The promising zone was defined as achieving or surpassing an average improvement in COVID-19 patient recoveries of 29% (hazard ratio (HR) > 1.29) or better through day 28. Humanigen believes, based on the recommended number of events the DSMB provided, the HR is approximately 1.37. Clearly, lenzilumab was has a positive effect on COVID-19 patient recovery. We at that time estimated that the topline readout would be delayed from YE2020 to early-2021. Humanigen intends to file for EUA in 1Q21 either after an interim analysis after 75% of events occurred or at study completion,” the Roth Capital analyst wrote. Roth Capital added that the next interim analysis for efficacy is planned when the study reaches 75% of events (302 events) which will require approximately 390 patients to be enrolled in the trial. The trial was being conducted in more than 20 sites total in the U.S., Brazil, and Mexico and Humanigen is working on quickly activating additional sites across the U.S. Roth Capital maintained its Buy rating on Humanigen with a $25 per share price target, based upon its estimated risk-adjusted 2021 revenue for lenzilumab of approximately $700 million.    What the boss says: Commenting on the company's 3Q 2020 operational results, Humanigen CEO Cameron Durrant said in a statement: “We’ve achieved many important milestones in the third quarter, including completing a public offering to begin trading on Nasdaq, being selected for the National Institutes of Health’s ACTIV-5/Big Effect Trial, strengthening our management team, adding clinical trial sites in Brazil for our Phase 3 clinical trial of lenzilumab in patients with COVID-19, and expanding our manufacturing capacity with new agreements with Catalent and Thermo Fisher.” He added: “For the last two months of 2020, we remain focused on enrollment of the Phase 3 trial of lenzilumab for patients hospitalized with COVID-19, in which we recently announced a positive analysis of interim Phase 3 data. As enrollment continues for this trial within the United States and in Brazil, we anticipate applying for an EUA in the first quarter of 2021. I’m pleased with how our team has remained dedicated to advancing promising therapeutics for cytokine storm and would like to thank the dedicated health care providers and essential workers who continue to expose themselves to risk during this pandemic.” Contact Sean at sean@proactiveinvestors.com