TET2

OSLO, Norway, Dec. 19, 2023 /PRNewswire/ -- Hemispherian AS ("Hemispherian" or the "Company"), a Norwegian preclinical pharmaceutical company focused on small molecule cancer therapeutics has been granted NOK 16 million by the Research Council of Norway. Hemispherian's proprietary GLIX compounds target a novel mechanism that is common to all cancers. The company's lead drug candidate, GLIX1, is in late-stage preclinical development for the treatment of glioblastoma, a highly aggressive and most common primary brain cancer, which continues to be one of the highest unmet needs in oncology. The funding awarded is earmarked for the development of Hemispherian's promising drug candidates aimed at treating platinum-resistant ovarian cancers, one of the most challenging gynecological malignancies. "We are immensely grateful for this support from the Research Council of Norway," said Zeno Albisser, CEO of Hemispherian. "Our team is excited to advance our second asset, GLIX5, towards clinical use. We are dedicated to developing therapies that will make a tangible difference in the lives of those battling cancer." About Hemispherian AS Hemispherian is an innovative pharmaceutical company focused on developing a novel class of small molecule drugs (GLIX). GLIX compounds target the TET2 enzyme and activate the DNA damage response resulting in cancer cell death. The company's lead compound, GLIX1, is in late-stage preclinical development for the treatment of glioblastoma, a deadly cancer of the central nervous system and the leading cause of death by disease in children. Hemispherian's further advances GLIX5 for the treatment of platinum-resistant ovarian cancers. Hemispherian is based in Oslo, Norway. For more information, visit . Contact: Zeno Albisser, CEO Gaustadalléen 21 0349 Oslo zeno@hemispherian.com +47 406 03 455 SOURCE Hemispherian AS

FOSTER CITY, Calif.--( BUSINESS WIRE )--Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, today announced new data and analyses from IMerge Phase 3 reporting robust durability of transfusion independence (TI), evidence for disease-modifying activity and favorable fatigue patient-reported outcomes (PRO) in lower risk myelodysplastic syndromes (MDS) patients treated with the Company’s first-in-class telomerase inhibitor, imetelstat, vs. placebo. The data and analyses were presented at the European Hematology Association (EHA) Annual Meeting, which took place from June 8-11, 2023 in Frankfurt, Germany and virtually. “ The new IMerge Phase 3 data and analyses presented at EHA continue to support the unprecedented and differentiating attributes of imetelstat, including 24-week transfusion independence across key MDS subgroups, potential disease-modifying activity, as well as favorable patient-reported outcomes (PRO) data on meaningful improvement in fatigue,” said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron. “ Each of these qualities address important unmet needs for lower risk MDS patients due to the limitation of current treatment options. Submission of our New Drug Application later this month is a significant step to hopefully bring imetelstat to these transfusion burdened patients.” Presentation Title: Continuous Transfusion Independence with Imetelstat in Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes Relapsed/Refractory to Erythropoiesis Stimulating Agents in IMerge Phase 3 Top-line results from the primary analysis of IMerge Phase 3 presented earlier this month at the 2023 American Society of Hematology (ASCO) Annual Meeting were also covered in the EHA presentation, including the primary endpoint of 8-week transfusion independence (TI) and key secondary endpoint of 24-week TI were met with high statistical significance (P<0.001) for imetelstat-treated patients vs. placebo. Further, mean hemoglobin levels in imetelstat-treated patients increased significantly (P<0.001) over time compared to placebo patients. In addition to these results, the EHA presentation also provided new data and analyses highlighting clinically meaningful and durable TI for imetelstat-treated patients vs. placebo. As of a January 2023 data cut-off, 17.8% (21/118) of imetelstat-treated patients vs. 1.7% (1/60) of placebo-treated patients achieved 1-year TI (P=0.002), representing 63.6% of 24-week TI imetelstat responders. Two new analyses presented at EHA on TI responses by subgroups underscored the breadth of potential effect of imetelstat vs. placebo. The first analysis reported higher durability of TI for imetelstat-treated patients vs. placebo across key MDS subgroups: Durability of RBC-TI for 8-Week TI Responders Across Key LR MDS Subgroups Imetelstat median, weeks (95% CI) Placebo median, weeks (95% CI) Hazard ratio (95% CI) P-value Overall 51.6 (26.9–83.9) 13.3 (8.0–24.9) 0.23 (0.09–0.57) <0.001 WHO category RS+ 46.9 (25.9–83.9) 16.9 (8.0–24.9) 0.32 (0.11–0.95) 0.035 RS- 51.6 (11.9–NE) 11.2 (10.1–NE) 0.11 (0.01–1.43) 0.062 Prior RBC transfusion burden per IWG 2006 4–6 units/8 weeks 51.9 (24.9–122.9) 16.9 (10.1–24.9) 0.35 (0.13–0.96) 0.035 6 units/8 weeks 39.9 (15.9–NE) 8.4 (8.0–NE) 0.04 (0.003–0.48) <0.001 IPSS risk category Low 43.9 (25.0–NE) 15.1 (8.0–24.9) 0.26 (0.10–0.68) 0.004 Intermediate-1 51.6 (11.9–NE) 10.1 (NE–NE) 0.15 (0.01–2.47) 0.128 Baseline sEPO ≤500 mU/mL 51.6 (26.9–83.9) 13.3 (8.0–24.9) 0.21 (0.075–0.61) 0.002 >500 mU/mL 122.9 (8.14–NE) 14.6 (12.3–NE) 0.34 (0.03–3.85) 0.364 Prior ESA use Yes 43.9 (26.9–80.0) 13.3 (8.0–24.9) 0.26 (0.10–0.72) 0.006 No 122.9 (8.14–NE) 14.6 (12.3–NE) 0.34 (0.03–3.85) 0.364 ____________________ Data cut-off: October 13, 2022. Hazard ratio (95% CI) from the Cox proportional hazard model, stratified by prior RBC transfusion burden (≥4 to ≤6 vs >6 RBC units/8 weeks during a 16-week period prior to randomization) and baseline IPSS risk category (low vs intermediate-1), with treatment as the only covariate. P -value (2-sided) for superiority of imetelstat vs placebo in hazard ratio based on stratified log-rank test. ESA, erythropoiesis-stimulating agent; IPSS, International Prognostic Scoring System; IWG, International Working Group; LR-MDS, lower-risk myelodysplastic syndromes; NE, not estimable; RBC, red blood cell; RS, ring sideroblast; sEPO, serum erythropoietin; TI, transfusion independence. The second analysis reported higher 24-week TI for imetelstat-treated patients vs. placebo across key MDS subgroups: Comparable 24-Week RBC-TI Rate Across Key LR MDS Subgroups Imetelstat n/N (%) Placebo, n/N (%) % Difference (95% CI) P-value Overall 33/118 (28.0) 2/60 (3.3) 24.6 (12.64–34.18) <0.001 WHO category RS+ 24/73 (32.9) 2/37 (5.4) 20.5 (−0.03–35.75) 0.003 RS- 9/44 (20.5) 0/23 (0.0) 0.11 (0.01–1.43) 0.019 Prior RBC transfusion burden per IWG 2006 4–6 units/8 weeks 19/62 (30.6) 2/33 (6.1) 24.6 (5.68–38.66) 0.006 6 units/8 weeks 39.9 (15.9–NE) 8.4 (8.0–NE) 0.04 (0.003–0.48) <0.001 IPSS risk category Low 23/80 (28.8) 2/39 (5.1) 23.6 (7.23–35.75) 0.003 Intermediate-1 10/38 (26.3) 0/21 (0) 26.3 (3.46–43.39) 0.009 Baseline sEPO ≤500 mU/mL 29/87 (33.3) 2/36 (5.6) 27.8 (10.46–39.71) 0.002 >500 mU/mL 4/26 (15.4) 0/22 (0) 15.4 (−5.81–35.73) 0.050 Prior ESA use Yes 31/108 (28.7) 2/52 (3.8) 24.9 (11.61–35.00) <0.001 No 2/10 (20) 0/8 20.0 (-23.47–55.78) 0.225 _____________ Data cut-off: October 13, 2022. 95% CI based on Wilson Score method. P -value determined by the Cochran-Mantel-Haenszel test, with stratification for prior RBC transfusion burden (≥4 to ≤6 vs >6 RBC units/8 weeks during a 16-week period prior to randomization) and baseline IPSS risk category (low vs intermediate-1) applied to randomization. ESA, erythropoiesis-stimulating agent; IPSS, International Prognostic Scoring System; IWG, International Working Group; LR-MDS, lower-risk myelodysplastic syndromes; RBC, red blood cell; RS, ring sideroblast; sEPO, serum erythropoietin; TI, transfusion independence. Additionally, the rate of 24-week TI was higher with imetelstat vs. placebo regardless of baseline mutation status, telomerase activity (TA), telomerase length (TL), and human telomerase reverse transcriptase (hTERT). “ For the first time at EHA, we see comparable 24-week TI across key MDS subgroups, which is especially meaningful for patients without ring sideroblasts (RS-) and very heavily transfusion burdened patients, who particularly have limited options today,” said Uwe Platzbecker, M.D., Department of Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany, who presented the data at EHA and is an IMerge investigator. “ In addition to the durability of TI, imetelstat-treated patients also achieved significant increases in hemoglobin and reductions of transfusion units that could be life changing for lower risk MDS patients, who often present with symptomatic anemia and transfusion dependence.” As previously reported, the safety profile observed with imetelstat in IMerge Phase 3 was consistent with prior clinical experience with no new safety signals. The EHA presentation provided new data on the consequences of the grade 3-4 thrombocytopenia and neutropenia which were most often reported during Cycles 1-3 and led to dose modifications. While approximately 50% of patients treated with imetelstat had dose reductions due to treatment emergent adverse events (TEAE), less than 15% of patients discontinued treatment due to TEAE. Discontinuation of imetelstat treatment in these patients due to a TEAE generally occurred late in treatment, with a median time to treatment discontinuation of 21.1 weeks (range 2.3 to 44.0 weeks). Presentation Title: Disease-Modifying Activity of Imetelstat in Patients with Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes Relapsed/Refractory to Erythropoiesis Stimulating Agents in IMerge Phase 3 “ In IMerge Phase 3, not only did we observe efficacy with imetelstat across the spectrum of genetic mutations associated with lower risk MDS, but we also saw a reduction in mutation burden, as measured by variant allele frequency (VAF). Furthermore, greater reduction of VAF in multiple genes correlated with the clinical endpoints of TI response, longer TI duration and increase in hemoglobin levels, suggesting the potential of imetelstat to modify the disease. This is the first therapy we know of that may alter the underlying biology of lower risk MDS by potentially reducing or eliminating malignant clones and improving ineffective erythropoiesis,” said Valeria Santini, M.D., MDS Unit, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy, who presented the data at EHA and is an IMerge investigator. In the EHA presentation, new data on cytogenetic responses and reductions in bone marrow RS supported the telomerase inhibition mechanism of action (MOA) of imetelstat. Among patients with cytogenetic abnormalities at baseline, the cytogenetic response rate was 35% (9/26) in imetelstat-treated patients and 15% (2/13) in the placebo group. Among cytogenetic responders, 89% (8/9) of patients in the imetelstat group and 50% (1/2) in the placebo group also achieved 8-week TI. A higher percentage of patients treated with imetelstat (40.8%) vs. placebo (9.7%) had a ≥50% reduction in central bone marrow RS. TI responses were enriched in patients achieving a ≥50% reduction in central bone marrow RS. Furthermore, the EHA presentation provided updated data on VAF reductions and new analyses on the correlation of such reductions with clinical responses which further support the potential disease-modifying activity of imetelstat. Reductions in variant allele frequency (VAF) of genes frequently mutated in MDS were greater for imetelstat-treated patients than placebo: SF3B1 (P< 0.001), TET2 (P= 0.032), DNMT3A (P= 0.019) and ASXL1 (P= 0.146). More patients treated with imetelstat vs. placebo had ≥50% VAF reduction in these mutations. For patients with the SF3B1 mutation, 29.5% (23/78) of those treated with imetelstat vs. 2.6% (1/38) on placebo (P=0.001) had a ≥50% VAF reduction. Imetelstat treatment resulted in sustained reduction of SF3B1 VAF over time. In the imetelstat group, 83% (19/23) of patients had 8-week TI among patients who achieved ≥50% maximum reduction from baseline in SF3B1 VAF vs. 38% (21/55) of those who did not. Similarly, TI responders were also enriched in imetelstat-treated patients achieving ≥50% reduction in TET2 VAF. In the imetelstat group, 83% (10/12) of patients had 8-week RBC-TI among patients who achieved ≥50% maximum reduction from baseline in TET2 VAF vs 43% (10/23) of those who did not. In imetelstat-treated patients, 24-week and 1-year TI responders were enriched in patients achieving ≥50% reduction in SF3B1 and TET2 VAF. VAF reduction in SF3B1, TET2 and DNMT3A correlated with longer TI duration and increases in hemoglobin levels in imetelstat-treated patients. Further, 8-week and 24-week TI correlated with reduction in RS+ cells, cytogenetic responses and VAF reduction. These correlations suggest the disease-modifying activity of imetelstat. Presentation Title: Analysis of Patient-Reported Fatigue in IMerge Phase 3 Trial of Imetelstat vs. Placebo in Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes Relapsed/Refractory to Erythropoiesis Stimulating Agents (ESA) “ The patient-reported outcome data from IMerge Phase 3 is particularly important as fatigue is a concern for lower risk MDS patients, most of whom are elderly. Furthermore, many of the current treatments for these patients cause fatigue. It is therefore very welcome news that imetelstat-treated patients showed sustained meaningful improvement in patient-reported fatigue vs. placebo. This is the first Phase 3 trial we know of to show an improvement in fatigue in lower risk MDS patients,” stated Dr. Platzbecker. The EHA presentation described results from an exploratory analysis from IMerge Phase 3 of patient-reported fatigue conducted using Functional Assessment of Chronic Illness Therapy, or FACIT, a validated 13-item patient questionnaire. The analysis reported imetelstat-treated patients were more likely to have sustained meaningful improvement in fatigue, as well as experience such improvement more quickly. Patients treated with imetelstat reported a lower rate of sustained meaningful deterioration in fatigue than placebo (43.2% vs 45.6%), while also receiving fewer transfusion units over time. For patients treated with imetelstat, there was a numerically higher percentage of patients reporting any episode of sustained meaningful improvement in fatigue. Further, patients receiving imetelstat experienced a shorter median time to first sustained clinically meaningful improvement in fatigue vs placebo (28.3 vs 65.0 weeks). For patients treated with imetelstat, there were significant associations between sustained meaningful improvement in fatigue and 8- and 24-week TI and HI-E response rates, an association not seen in the placebo group. Additional analysis showed that patients experiencing grade 3 or 4 neutropenia or thrombocytopenia had the same rates of sustained meaningful improvement in fatigue (52.5% and 53.4%, respectively) as the total imetelstat population (50%). Additional Presentations at EHA In addition to these IMerge Phase 3 presentations, Geron collaborators presented a translational analysis from a subset of IMerge Phase 2 patients, as well as imetelstat myelofibrosis (MF) pre-clinical results. The presentation slides and posters are available on the Publications section of Geron’s website: https://www.geron.com/research-and-development/publications/ . About IMerge Phase 3 The Phase 3 portion of the IMerge Phase 2/3 study is a double-blind, 2:1 randomized, placebo-controlled clinical trial to evaluate imetelstat in patients with IPSS Low or Intermediate-1 risk (lower risk) transfusion dependent MDS who were relapsed after, refractory to, or ineligible for, erythropoiesis stimulating agent (ESA) treatment, had not received prior treatment with either a HMA or lenalidomide and were non-del(5q). To be eligible for IMerge Phase 3, patients were required to be transfusion dependent, defined as requiring at least four units of packed red blood cells (RBCs), over an eight-week period during the 16 weeks prior to entry into the trial. The primary efficacy endpoint of IMerge Phase 3 is the rate of red blood cell transfusion independence (RBC-TI) lasting at least eight weeks, defined as the proportion of patients without any RBC transfusion for at least eight consecutive weeks since entry to the trial (8-week TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week TI), the duration of TI and the rate of hematologic improvement erythroid (HI-E), which is defined under 2006 IWG criteria as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least eight weeks or a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden. A total of 178 patients were enrolled in IMerge Phase 3 across North America, Europe, Middle East and Asia. About Imetelstat Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from non-clinical studies and clinical trials of imetelstat provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of adult patients with transfusion dependent anemia due to Low or Intermediate-1 risk MDS that is not associated with del(5q) who are refractory or resistant to an erythropoiesis stimulating agent, and for adult patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment. Geron plans to submit a New Drug Application (NDA) in the U.S. in June 2023 and a Marketing Authorization Application (MAA) in the EU in the second half of 2023 in the lower risk MDS indication. About Geron Geron is a late-stage biopharmaceutical company pursuing therapies with the potential to extend and enrich the lives of patients living with hematologic malignancies. Our first-in-class telomerase inhibitor, imetelstat, harnesses Nobel Prize-winning science in a treatment that may alter the underlying drivers of disease. Geron currently has two Phase 3 pivotal clinical trials underway evaluating imetelstat in lower risk myelodysplastic syndromes (LR MDS), and in relapsed/refractory myelofibrosis (MF). To learn more, visit www.geron.com or follow us on LinkedIn . Use of Forward-Looking Statements Except for the historical information contained herein, this press release contains forward-looking statements made pursuant to the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such statements, include, without limitation, those regarding: (i) that for IMerge Phase 3, Geron plans to submit a New Drug Application in the U.S. in June 2023 and a Marketing Authorization Application in the EU in the second half of 2023; (ii) a potential U.S. commercial launch of imetelstat for lower risk MDS in the first half of 2024; (iii) that imetelstat may alter the underlying biology of lower risk MDS and has the potential to demonstrate disease-modifying activity in patients; and (iv) other statements that are not historical facts, constitute forward-looking statements. These forward-looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties, include, without limitation, risks and uncertainties related to: (a) whether the current or evolving effects of the COVID-19 pandemic and/or geopolitical events and resulting global economic and financial disruptions will materially and adversely impact Geron’s business and business prospects, its financial condition and the future of imetelstat; (b) whether Geron overcomes all of the potential delays and other adverse impacts caused by the current or evolving effects of the COVID-19 pandemic and/or geopolitical events, as well as all the enrollment, clinical, safety, efficacy, technical, scientific, intellectual property, manufacturing and regulatory challenges in order to have the financial resources for, and to meet the expected timelines, planned milestones and expenses; (c) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (d) whether imetelstat has demonstrated sufficient safety, efficacy and clinical benefit in IMerge Phase 3 to enable regulatory approval; (e) whether any future safety or efficacy results cause the benefit-risk profile of imetelstat to become unacceptable; (f) whether imetelstat actually demonstrates that it alters the underlying biology of lower risk MDS and has disease-modifying activity in patients;; (g) that Geron may seek to raise substantial additional capital in order to complete the development and commercialization of imetelstat to meet the expected timelines, planned milestones and expenses; (h) whether there are failures or delays in manufacturing or supplying sufficient quantities of imetelstat or other clinical trial materials that impact a commercial launch in lower risk MDS; (i) whether the follow-up period of 12 months for the IMerge Phase 3 primary analysis was sufficient to demonstrate safety and efficacy, including transfusion independence and clinical benefit, and obtain regulatory approval; and (j) for IMerge Phase 3, the FDA may require Geron to submit additional information or require advisory committee procedures that could cause a regulatory approval, if any, to be delayed. Additional information on the above risks and uncertainties and additional risks, uncertainties and factors that could cause actual results to differ materially from those in the forward-looking statements are contained in Geron’s filings and periodic reports filed with the Securities and Exchange Commission under the heading “Risk Factors” and elsewhere in such filings and reports, including Geron’s quarterly report on Form 10-Q for the quarter ended March 31, 2023 and future filings and reports by Geron. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events or circumstances.

- Of the 14 participants enrolled and treated with lenzilumab plus azacitidine, ten are evaluable with three to eighteen months of follow-up and all ten have had a rapid clinical response - Building upon previously reported positive clinical responses, these additional data demonstrate statistically significant and clinically relevant improvements in hematologic outcomes, along with improvements in inflammatory markers, that occur in the early months after treatment initiation and appear durable - CMML is a rare, aggressive cancer; approximately 20% of patients survive three years from diagnosis - No new CMML medications with novel mechanisms of action have been approved in over 30 years and hypomethylating agents, such as azacitidine alone, are currently considered “standard of care” Short Hills, New Jersey – (June 9, 2023) - Humanigen, Inc. (Nasdaq: HGEN) today extended previously reported results by presenting additional, statistically significant hematologic improvements and reductions in inflammatory markers from lenzilumab, its investigational drug, in a Phase 2/3 trial of treatment-naïve participants with chronic myelomonocytic leukemia and RAS-pathway mutations. The additional data demonstrate that in all 10 participants with at least three months of treatment with both lenzilumab and azacitidine, blood monocyte count decreased fivefold (P=0.03), the percentage of blast cells and pro-monocytes decreased more than twofold (P=0.04), and C-reactive protein decreased more than threefold (P=NS) with improvements noted after both 3 months and 6 months of this combination treatment. These results suggest lenzilumab may normalize hematologic and inflammatory aberrations in CMML and improve the condition of participants. All ten evaluable participants had a rapid clinical response. CMML is a rare, aggressive cancer in which levels of monocytes, blast cells, and pro-monocytes are significantly elevated from normal levels. These pathologic changes are accompanied by significantly elevated proinflammatory markers, including C-reactive protein. Current treatment options for CMML patients are limited to blood transfusions, hydroxyurea, and supportive care alongside the current standard of care, which includes hypomethylating agents such as azacitidine and decitabine, which have limited response rates of 7% to 18%1, 2, 3 with no proven increase in overall survival. In the last 30 years, no new medicines with a novel mechanism of action have been approved for CMML patients who are at high risk of death or disease progression.4 Only about 20% of patients diagnosed with CMML survive for three years.5 “The PREACH-M trial findings to date, indicate that lenzilumab may improve treatment response in CMML,” said Humanigen Chairman and CEO Cameron Durrant, MD, MBA. “These results may create the possibility for lenzilumab development in myelodysplastic leukemias. I look forward to sharing the data at the poster presentation at the 2023 European Hematology Association congress in Frankfurt, Germany.” The presentation, entitled “Lenzilumab and Azacitidine Improve Hematologic Alterations of Chronic Myelomonocytic Leukemia in the PREACH-M Trial,” highlighted new data in poster format (P737) at 6:00 pm CEST on June 9, 2023, during the 2023 European Hematology Association congress. “Patients with CMML are normally treated with hypomethylating agents such as azacitidine, with reported response rates of just 7% to 18%, usually of limited duration,” said principal investigator Daniel Thomas, MD, PhD, program leader for blood cancer research at SAHMRI and an associate professor of medicine at the University of Adelaide. “Treating patients with lenzilumab appears to be improving clinical parameters, quality of life and systemic inflammation in the patients studied so far, and patients appear to be tolerating lenzilumab well. Critically, clinical responses appear to occur early, prior to the fourth monthly treatment cycle. No patients have relapsed, and we currently have two patients remaining on treatment for more than 18 months.” Lenzilumab, a granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralizing antibody, prevents GMCSF from binding to receptors on hematologic progenitor cells. When GM-CSF binds to those receptors, it triggers normal myelocyte proliferation and maturation. In the presence of RAS-pathway mutations, GM-CSF contributes to the hyperproliferation of myelocytes in myelodysplastic leukemias such as CMML, juvenile myelomonocytic leukemia (JMML), and acute myeloid leukemia (AML).6,7,8 Therefore, lenzilumab’s ability to prevent GM-CSF binding to its receptor may inhibit the hyperproliferation in these conditions. PREACH-M (PREcision Approach to CHronic Myelomonocytic Leukemia), a non-randomized, open-label trial, is being conducted at multiple sites in Australia. It is sponsored by the South Australian Health and Medical Research Institute (SAHMRI), with grant funding from the Australian government and the study drug supplied by Humanigen. As of May 9, 2023, 14 CMML patients at intermediate or high risk of death or disease progression have received at least one dose of lenzilumab, along with azacitidine. Ten of those participants were evaluable based on at least three months of follow-up, and each experienced a rapid clinical benefit. Twenty-one grade 3 or 4 serious adverse events were observed, of which investigators assessed five as possibly related to lenzilumab. +++ About CMML CMML is an orphan disease with an approximate annual incidence of 1-4 cases per million1 in western countries and has limited therapeutic options. CMML is an aggressive and poorly understood cancer with only about 20% of patients surviving up to the three-year mark.9 The incidence of CMML in the US, UK, and Australia is about 1,700 patients annually.9 As an orphan disease, lenzilumab may qualify for certain regulatory and commercial advantages that could expedite development and potential approval. Humanigen and the Principal Investigator are assessing regulatory pathways that may enable early results to support a regulatory submission and potential approval by the Therapeutic Goods Administration in Australia, which could be expanded through Project Orbis10 to the United States and the United Kingdom ( ). About the PREACH-M Trial PREACH-M (PREcision Approach to CHronic Myelomonocytic Leukemia) is a Phase 2/3, non-randomized, openlabel clinical trial investigating precision medicine for adults with CMML.11 This trial investigates treatment response rates determined by the Savona Criteria for patients with CMML after administration of lenzilumab alongside azacitidine in patients with RAS pathway mutations. The study also measures the patients’ quality of life, using the MPN Symptoms Assessment Form: Total Symptom Score. Fourteen study participants were enrolled and treated with lenzilumab and azacitidine as of May 9, 2023, of which ten were evaluable for hematologic and inflammatory parameters based on at least three months of follow-up. The initial data demonstrate that blood monocyte count decreased by fivefold (p=0.03), percentage of blast cells and pro-monocytes decreased by more than twofold (p=0.04), platelet count and hemoglobin concentration both increased and remained elevated at 12 months (p=0.07 and p=0.02, respectively), and craniocaudal spleen size decreased by nearly 50% by 6 months (p=0.03). The inflammatory marker, C-reactive protein decreased by more than threefold (p=NS). All ten evaluable participants had a rapid clinical response. During the active treatment phase of the study, participants are required to attend clinic visits on Days 1 & 15 of the first cycle, and then on Day 1 of each subsequent 28-day cycle to assess how the participant is tolerating the therapy and ensure ongoing safety.12 In addition to regular safety blood tests throughout each cycle, participants’ disease response assessments are scheduled after 3, 6, 12 and 24 cycles of therapy to measure their disease response.12 Such assessments include blood tests, bone marrow aspirate and trephine, ultrasound of the spleen, physical exam and assessment of transfusion requirements and clinical symptoms.12 Participants who complete 24 cycles of active treatment enter the follow-up phase of the study where they are followed up every 6 months for 24 months for survival, disease status and further CMML-related treatment.11 For patients with confirmed progressive disease or relapse during the active treatment phase of the study, further study treatment will cease. Patients remain on study and are followed up for disease status, survival, and further CMML-related treatment every 6 months until 48 months from Cycle 1, Day 1.11 During the follow-up period, participants no longer receive any investigational drugs but are permitted to receive any CMML treatment at the discretion of the treating clinician. As part of the screening process, participants are required to have a bone marrow aspirate and trephine to test for certain acquired mutations that can be present in CMML.11 The study is seeking participants with TET2 and/or RAS pathway mutations. Participants with RAS pathway mutations or both TET2 and RAS mutations, receive azacitidine (administered subcutaneously at a dose of 75mg/m2 on Days 1-5, 8-9 or Days 1-7 for a total of 7 doses per 28-day cycle) in combination with lenzilumab (administered intravenously at a dose of 552mg on Days 1 & 15 of Cycle 1. Day 1 only for all subsequent cycles).11 The trial is sponsored by the South Australian Health and Medical Research Institute (“SAHMRI”) and funded by a Medical Research Future Fund grant from the National Health and Medical Research Council of the Australian government to the University of Adelaide. Humanigen provides lenzilumab for use in the study through its Australian subsidiary, Humanigen Australia Pty Ltd. Enrollment is open to newly diagnosed CMML patients who haven’t received any treatment. Anyone who is interested in learning more about the study, or obtaining additional information can visit the Australian New Zealand Clinical Trials Registry ( ). About Humanigen Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), is a clinical-stage biopharmaceutical company focused on developing lenzilumab, a first-in-class antibody that binds to and neutralizes granulocyte-macrophage colonystimulating factor. Humanigen is developing lenzilumab as a treatment for chronic myelomonocytic leukemia. Humanigen is also exploring the use of lenzilumab to prevent toxicities associated with CAR-T therapy through investigator-initiated trials. Humanigen is also developing an antibody drug conjugate (ADC) utilizing its EphA-3 targeted monoclonal antibody ifabotuzumab ("ifab") for solid tumors. For more information, visit About the European Hematology Association The European Hematology Association serves medical professionals, researchers, and scientists with an active interest in hematology. They are the largest European-based organization connecting hematologists worldwide to support career development and research, harmonize hematology education, and advocate for hematologists and hematology. About the EHA Hybrid Congress The EHA2023 Hybrid Congress, being held in Frankfurt, Germany, from June 8-11, 2023, offers an interactive, comprehensive program dedicated to clinical research and practice, basic and translational research, as well as important opportunities for collaboration with stakeholders in the field of hematology. The educational and scientific program highlights state-of-the-art clinical practice, the latest findings in hematology research, and recent approaches on the diagnosis and treatment of hematologic diseases. Forward-Looking Statements about Humanigen All statements other than statements of historical facts contained in this press release are forward-looking statements. Forward-looking statements reflect management's current knowledge, assumptions, judgment, and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct, and you should be aware that actual events or results may differ materially from those contained in the forward- looking statements. Words such as "will," "expect," "intend," "plan," "potential," "possible," "goals," "accelerate," "continue," and similar expressions identify forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to, the risks inherent in our lack of profitability and need for additional capital to continue as a going concern; our dependence on partners to further the development of our product candidates; the uncertainties inherent in the development, attainment of the requisite regulatory authorizations and approvals and launch of any new pharmaceutical product; the outcome of pending or future litigation or arbitration; and the various risks and uncertainties described in the "Risk Factors" sections of our latest annual and quarterly reports and other filings with the SEC. All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You should not rely upon any forward-looking statements as predictions of future events. We undertake no obligation to revise or update any forward-looking statements made in this press release to reflect events or circumstances after the date hereof, to reflect new information or the occurrence of unanticipated events, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, in each case, except as required by law. Humanigen Investor Relations Contact Ed Jordan Chief Commercial Officer IR@humanigen.com 650-243-3181 Humanigen Media Relations Contact Charlotte Wray cwray@rxmedyn.com 646-247-3405 References 1. Costa, R., et. al. (2010). Activity of azacitidine in chronic myelomonocytic leukemia. Cancer, 117(12), 2690– 2696. 2. South Australian Registry data, South Australian Health and Medical Research Institute, April 14, 2021 3. Pleyer, L., et. al. (2014). Azacitidine in CMML: Matched-pair analyses of daily-life patients reveal modest effects on clinical course and survival. Leukemia Research, 38(4), 475–483. 4. Aim of first-ever CMML study – to improve survival. Leukaemia Foundation. (2023, January 3). Retrieved January 3, 2023, from survival/ 5. Ma, L., Jiang, L., Yang, W., Luo, Y., Mei, C., Zhou, X., Xu, G., Xu, W., Ye, L., Ren, Y., Lu, C., Lin, P., Jin, J., & Tong, H. (2021). Real-world data of chronic myelomonocytic leukemia: A chinese single-center retrospective study. Cancer medicine, 10(5), 1715–1725. 6. Gupta, A. et al. (2021). Juvenile myelomonocytic leukemia-A comprehensive review and recent advances in management. American Journal of Blood Research, 11(1), 1–21. Retrieved July 21, 2022, from 7. Padron, E., et al. (2013). GM-CSF–dependent PSTAT5 sensitivity is a feature with therapeutic potential in chronic myelomonocytic leukemia. Blood, 121(25), 5068–5077. 460170 8. Emanuel, P. D., et al. (1991). Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors. Blood, 77(5), 925–929. 9. Incidence extrapolated by applying NIH SEER incidence rate of five per one million people found at to the population of U.S., UK, and Australia, Prevalence data also from NIH SEER. 10. U.S. Food and Drug Administration. A framework for concurrent submission and review of Oncology Products. Retrieved March 20, 2023, from excellence/project-orbis 11. Australian New Zealand Clinical Trials Registry. Retrieved March 20, 2023, from 12. Preach-M: Precision medicine for chronic myelomonocytic leukaemia in adults: A phase II trial studying the efficacy of lenzilumab and high dose ascorbate with azacitidine based on molecular profiling. PREACH-M - Victorian Cancer Trials Link. (n.d.). Retrieved January 3, 2023, from