On March 10, 2022 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company developing a first-in-class telomerase inhibitor, imetelstat, to treat hematologic malignancies, reported business updates, upcoming milestones and financial results for the fourth quarter and year ended December 31, 2021 (Press release, Geron, MAR 10, 2022, View Source [SID1234609887]). The Company ended 2021 with $212.7 million in cash and marketable securities, which the Company believes is sufficient to fund current operations through the end of the first quarter of 2023.

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"We made significant accomplishments in 2021 to advance the development of imetelstat toward two important Phase 3 data readouts, which if positive, have the potential to transform patient care in lower risk MDS and refractory MF," said John A. Scarlett, M.D., Chairman and Chief Executive Officer. "With completion of enrollment in IMerge Phase 3 last October, we look forward to top-line results from that trial in early January 2023. If those results confirm similar safety, as well as the depth, breadth and durability of transfusion independence that was observed in our Phase 2 trial, then upon approval of an NDA, we expect our U.S. commercial launch of imetelstat in lower risk MDS to occur as early as the first half of 2024."

Dr. Scarlett added, "In 2021, we also made progress with the IMpactMF Phase 3 trial in refractory MF, by opening 50% of the planned clinical sites to patient enrollment. In 2022, we plan to open the rest of the selected clinical sites to enable the planned interim analysis in 2024."

Dr. Scarlett also noted, "Building on the strong evidence of imetelstat’s disease modification potential from our Phase 2 trials, we started several new programs in 2021. We believe that the data to be generated from these programs over the next few years will provide strategic value to the imetelstat franchise through the potential expansion into new myeloid and lymphoid hematologic indications, as well as into combination regimens."

Key Upcoming Milestones Expected

Top-line results from IMerge Phase 3 in early January 2023
Open the rest of the selected clinical sites in IMpactMF for enrollment to enable the planned interim analysis in 2024
Expand into additional indications and treatment combinations:
Start of IMproveMF Phase 1 study of imetelstat + ruxolitinib in frontline MF in 1H 2022
Start of IMpress Phase 2 study of single-agent imetelstat in R/R AML and HR MDS in 2H 2022
Start of TELOMERE Phase 1/2 study of imetelstat + HMAs or venetoclax in R/R AML in 2H 2022
Top-Line Results Expected in Early January 2023 from IMerge Phase 3 in Lower Risk Myelodysplastic Syndromes (MDS)

Assuming the results of IMerge Phase 3 support regulatory submissions, Geron plans to submit a New Drug Application (NDA) in the United States in the first half of 2023 and a Marketing Authorization Application (MAA) in Europe in the second half of 2023 for imetelstat in lower risk MDS. Upon potential approval by the United States Food and Drug Administration (FDA) of the NDA, the Company expects that its commercial launch of imetelstat in lower risk MDS in the United States could occur as early as the first half of 2024.

Planned Interim Analysis in 2024 from IMpactMF in Refractory Myelofibrosis (MF)

IMpactMF, the only Phase 3 clinical trial in MF with overall survival (OS) as a primary endpoint, is planned to engage approximately 180 clinical sites across North America, South America, Europe, Australia and Asia to facilitate patient recruitment and enrollment into the trial. The Company expects to open for enrollment the remaining approximately 50% of selected clinical sites in 2022.

Under current planning assumptions around enrollment and median overall survival for each treatment arm, the Company expects to conduct the interim analysis in 2024 and the final analysis in 2025. The final analysis for OS is planned to be conducted after more than 50% of the patients enrolled in the trial have died. An interim analysis of OS is planned to be conducted after approximately 70% of the total projected number of events for the final analysis have occurred. If the pre-specified, statistically significant difference in OS between the two treatment arms is met at the interim analysis, it is possible that data from the interim analysis could support a registration filing. Both the planned interim and final analyses are event-driven and could occur on different timelines than currently expected.

Pipeline Expansion to Enhance Imetelstat Potential

In November 2021, the Company unveiled three new clinical programs and one preclinical program for imetelstat. These programs explore the use of imetelstat as a single agent and in combination with current standard of care therapies to expand the potential application of imetelstat.

In the first half of 2022, Geron plans to initiate IMproveMF, a company-sponsored Phase 1 study of imetelstat in combination with ruxolitinib in frontline MF patients. In addition, in collaboration with key opinion leaders with expertise in acute myeloid leukemia (AML), the Company is supporting investigator-led studies in relapsed/refractory AML and higher risk MDS (HR MDS) to evaluate imetelstat as a single agent and in combination with venetoclax or hypomethylating agents (HMAs). These studies are expected to start in the second half of 2022. The preclinical program in lymphoid malignancies is being conducted at MD Anderson Cancer Center, and the Company expects preliminary results from ongoing in vitro and in vivo experiments to be available by the end of 2022.

Fourth Quarter and Full Year 2021 Results

For the fourth quarter of 2021, the Company reported a net loss of $32.0 million, or $0.10 per share, compared to $23.8 million, or $0.07 per share, for the fourth quarter of 2020. Net loss for the full year of 2021 was $116.1 million, or $0.35 per share, compared to $75.6 million, or $0.28 per share, for the full year of 2020.

Revenues for the three and twelve months ended December 31, 2021 were $1.0 million and $1.4 million, respectively, compared to $50,000 and $253,000 for the same periods in 2020. Revenues in 2021 and 2020 primarily reflect estimated royalties from sales of cell-based research products from the Company’s divested stem cell assets. In connection with the 2013 divestiture of Geron’s human embryonic stem cell assets, including intellectual property and proprietary technology, to Lineage Cell Therapeutics, Inc. (formerly BioTime, Inc., which acquired Asterias Biotherapeutics, Inc.), Geron is entitled to receive royalties on sales from certain research or commercial products utilizing Geron’s former intellectual property. The increase in revenues in 2021 compared to 2020 primary reflects retroactive royalties of approximately $911,000 on product sales of cell-based research products.

Total operating expenses for the three and twelve months ended December 31, 2021 were $32.0 million and $115.4 million, respectively, compared to $23.3 million and $77.2 million for the same periods in 2020.

Research and development expenses for the three and twelve months ended December 31, 2021 were $24.2 million and $85.7 million, respectively, compared to $16.2 million and $51.5 million for the same periods in 2020. The increase in research and development expenses for the three and twelve months ended December 31, 2021, compared to the same periods in 2020, primarily reflects increased clinical development costs associated with conducting two Phase 3 clinical trials, higher imetelstat manufacturing costs for producing validation batches at contract manufacturers to enable future production of imetelstat for clinical and commercial purposes and higher personnel-related costs for additional headcount.

General and administrative expenses for the three and twelve months ended December 31, 2021 were $7.9 million and $29.7 million, respectively, compared to $7.1 million and $25.7 million, for the same periods in 2020. The increase in general and administrative expenses for the three and twelve months ended December 31, 2021, compared to the same periods in 2020, primarily reflects new costs in connection with pre-commercial activities, including modernizing the internal infrastructure to support a commercial launch, and higher legal costs.

Interest income for the three and twelve months ended December 31, 2021 was $106,000 and $527,000, respectively, compared to $243,000 and $1.8 million for the same periods in 2020. The decrease in interest income for the three and twelve months ended December 31, 2021, compared to the same periods in 2020, primarily reflects lower yields on the Company’s marketable securities portfolio.

Interest expense for the three and twelve months ended December 31, 2021 was $1.1 million and $3.7 million, respectively, compared to $754,000 and $760,000 for the same periods in 2020. In September 2020, the Company secured a new debt facility for up to $75 million. As of December 31, 2021, a total of $50 million has been drawn down under the facility.

Financial Resources and Projected 2022 Financial Guidance

The Company ended 2021 with $212.7 million in cash and marketable securities, which the Company believes is sufficient to fund current operations through the end of the first quarter of 2023.

For fiscal year 2022, under generally accepted accounting principles (GAAP), the Company expects total operating expenses in the range of approximately $155 million to $165 million, which includes non-cash items such as: stock-based compensation expense, amortization of debt discounts and issuance costs and depreciation and amortization. The Company expects non-GAAP total operating expenses for fiscal year 2022, which excludes estimated non-cash items such as: stock-based compensation expense, amortization of debt discounts and issuance costs and depreciation and amortization, in the range of approximately $140 million to $150 million.

The fiscal year 2022 financial guidance reflects costs to support preparatory activities for top-line results in lower risk MDS; NDA and commercial readiness; two ongoing Phase 3 clinical trials and new clinical studies expanding the pipeline; finalizing validation batches of imetelstat at contract manufacturers to enable future production of imetelstat for clinical and commercial purposes; projected increases in headcount and interest payments on outstanding debt.

As of December 31, 2021, the Company had 72 employees. The Company plans to grow to a total of approximately 90 to 100 employees by year-end 2022.

Conference Call

Geron will host a conference call at 4:30 p.m. ET on Thursday, March 10, 2022 to discuss business updates, expected upcoming milestones and fourth quarter and full year 2021 financial results.

A live webcast of the conference call and related presentation will be available on the Company’s website at www.geron.com/investors/events. An archive of the webcast will be available on the Company’s website for 30 days.

Participants may access the webcast by registering online using the following link, View Source Participants that are unable to register online can access the conference call via telephone by dialing domestically +1 (888) 330-2434 or internationally +1 (240) 789-2725. The conference ID is 67335.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from Phase 2 clinical trials 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 United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment.

About IMerge Phase 3

IMerge Phase 3 is a double-blind, randomized, placebo-controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 170 transfusion dependent patients with Low or Intermediate-1 risk myelodysplastic syndromes (MDS), also referred to as lower risk MDS, who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The primary endpoint is the rate of red blood cell (RBC) transfusion independence (TI) for any consecutive period of eight weeks or longer, or 8-week RBC-TI rate. Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks, or 24-week RBC-TI rate, duration of TI and the rate of hematologic improvement-erythroid (HI-E), defined as a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden.

IMerge Phase 3 is fully enrolled and patient enrollment has been closed. For additional information about IMerge Phase 3, visit ClinicalTrials.gov/NCT02598661.

About IMpactMF

IMpactMF is an open label, randomized, controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 320 patients with Intermediate-2 or High-risk myelofibrosis (MF) who are refractory to prior treatment with a JAK inhibitor, also referred to as refractory MF. Patients will be randomized to receive either imetelstat or best available therapy. The primary endpoint is overall survival (OS). Key secondary endpoints include symptom response, spleen response, progression free survival, complete remission, partial remission, clinical improvement, duration of response, safety, pharmacokinetics, and patient reported outcomes.

IMpactMF is currently enrolling patients. For further information about IMpactMF, including enrollment criteria, locations and current status, visit ClinicalTrials.gov/NCT04576156.