Geron Corporation, a late-stage biopharmaceutical company, is on the cusp of a significant milestone with its investigational first-in-class telomerase inhibitor, imetelstat. The company's sole product candidate, imetelstat, has demonstrated promising results in the treatment of hematologic malignancies, particularly in lower-risk myelodysplastic syndromes (MDS).

Business Overview

Geron is dedicated to developing therapies that have the potential to extend and enrich the lives of patients living with hematologic malignancies. The company's lead indication for imetelstat is in low or intermediate-1 risk MDS. In August 2023, Geron's New Drug Application (NDA) for the treatment of transfusion-dependent anemia in adult patients with low-to-intermediate-1 risk MDS who have failed to respond or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs) was accepted by the United States Food and Drug Administration (FDA) for review and assigned a Prescription Drug User Fee Act (PDUFA) action date of June 16, 2024.

Geron has also submitted a marketing authorization application (MAA) in Europe for imetelstat for the same proposed indication as in the U.S. The company expects a review of the MAA could be completed in early 2025, and subject to MAA review completion on that timing and ultimate approval of the MAA by the European Commission, Geron believes EU commercial launch of imetelstat would occur in 2025.

Geron's NDA and EMA submissions are based on positive data from the IMerge Phase 3 clinical trial. The trial met its primary endpoint of ≥ 8-week red blood cell transfusion independence rate and a key secondary endpoint of ≥ 24-week red blood cell transfusion independence rate, demonstrating highly statistically significant (i.e., p<0.001 for both) and clinically meaningful benefits with imetelstat treatment versus placebo.

In addition to lower-risk MDS, Geron is developing imetelstat for the treatment of several myeloid hematologic malignancies. The company's Phase 3 clinical trial IMpactMF evaluates imetelstat in patients with Intermediate-2 or High-Risk myelofibrosis who have relapsed after or are refractory to treatment with a janus associate kinase inhibitor (JAK inhibitor), or relapsed/refractory MF, with overall survival as the primary endpoint. In November 2023, the trial reached 50% enrollment. Based on Geron's current planning assumptions for enrollment and event (death) rates in the trial, the company expects the interim analysis for overall survival in IMpactMF may occur in early 2026, and the final analysis may occur in early 2027.

Geron is also conducting a Phase 1 combination therapy clinical trial, named IMproveMF, in first-line Intermediate-1, Intermediate-2 or High-Risk myelofibrosis, and an investigator-led Phase 2 clinical trial, named IMpress, in Intermediate-2 or High-Risk myelodysplastic syndromes and acute myeloid leukemia patients that are relapsed or refractory to hypomethylating agent treatment.

Financials

Geron has primarily financed its operations through the sale of equity securities, draw downs on its debt facility, interest income on its marketable securities and payments received under its prior collaborative and licensing arrangements. As of March 31, 2024, the company had approximately $465.0 million in cash, cash equivalents, restricted cash and current and noncurrent marketable securities and a long-term principal debt balance of $80.0 million.

For the full year 2023, Geron reported annual revenue of $237,000 and a net loss of $184,127,000. The company's annual operating cash flow was -$167,103,000 and annual free cash flow was -$167,933,000.

In the first quarter of 2024, Geron reported revenue of $304,000 and a net loss of $55,390,000. The company's operating cash flow was -$62,253,000 and free cash flow was -$62,868,000 for the quarter.

Based on Geron's current operating plan and assumptions regarding the timing of the potential approval and commercial launch of imetelstat in lower-risk MDS in the U.S., the company believes that its existing cash, cash equivalents, and current and noncurrent marketable securities, together with projected revenues from U.S. sales of imetelstat, if approved, potential proceeds from the exercise of outstanding warrants, and potential future drawdowns under the Loan Agreement, will be sufficient to fund its projected operating requirements into the second quarter of 2026.

Regulatory and Commercial Readiness

On March 14, 2024, the FDA convened its Oncologic Drugs Advisory Committee (ODAC) to discuss Geron's NDA for imetelstat for the treatment of transfusion-dependent anemia in adult patients with IPSS low-to intermediate-1 risk MDS who have failed to respond or have lost response to or are ineligible for ESAs. The ODAC discussed the efficacy of imetelstat in this proposed indication, based on the results of the IMerge Phase 3 clinical trial, considering the safety profile, and voted 12 to 2 that the benefits of imetelstat outweigh its risks in this proposed indication.

Geron is in the final stages of commercial readiness execution, which has included bringing on a sales force in April 2024. The company is also engaging in marketing, commercial access, payer and reimbursement preparatory efforts, as well as completing the build out of its enterprise capabilities and systems to support its transition to a commercial stage company.

Geron's market research suggests that imetelstat is highly differentiated in the transfusion-dependent low-risk MDS market. Medical and payer stakeholders have expressed enthusiasm for the totality of clinical benefits seen with imetelstat, including durable red blood cell transfusion independence, hemoglobin increases and reduction in transfusion burden, balanced with a generally well-characterized and manageable safety profile.

Geron believes imetelstat is uniquely positioned to address unmet needs in transfusion-dependent low-risk MDS, particularly for ESA-ineligible, ESA-fail RS-negative, and RS-positive high transfusion burden patients, which constitute approximately 75% of the market. The company expects to see imetelstat uptake across these patient populations upon potential approval.

Risks and Challenges

Geron's future success depends solely on imetelstat, its only product candidate. The company cannot be certain that it will be able to continue to develop imetelstat or advance it to subsequent clinical trials, or that it will be able to receive regulatory approval for or to commercialize imetelstat, on a timely basis or at all.

Imetelstat may cause, or have attributed to it, undesirable or unintended side effects or other adverse events that could further delay or prevent the commencement and/or completion of clinical trials for imetelstat, delay or prevent its regulatory approval, or limit its commercial potential.

If IMpactMF fails to demonstrate safety and effectiveness to the satisfaction of the FDA or international regulatory authorities, Geron would incur additional costs, experience delays in completing or ultimately fail in completing the development and commercialization of imetelstat in patients with relapsed/refractory MF, which would have a material adverse effect on the company's business, business prospects and the future of imetelstat.

Geron's clinical trials of imetelstat could be interrupted, delayed, terminated or abandoned for a variety of reasons, which could severely and adversely affect the company's financial results, business and business prospects, and the future of imetelstat.

If Geron is unable to obtain regulatory approval for and successfully commercialize imetelstat, including obtaining and maintaining licenses where required for the company to sell imetelstat, or experience significant delays in doing so, its business will be materially harmed.

Liquidity

As of March 31, 2024, Geron had cash, restricted cash, cash equivalents, and marketable securities of $465.0 million, compared to $378.1 million at December 31, 2023. The increase in cash, restricted cash, cash equivalents and marketable securities during the three months ended March 31, 2024 was primarily the net result of the receipt of net cash proceeds of $141.0 million from the company's underwritten offering completed in March 2024.

Geron may, from time to time, consider additional funding through a combination of new collaborative arrangements, strategic alliances, and additional equity and debt financings or from other sources. The company will continue to manage its capital structure and consider all financing opportunities, whenever they may occur, that could strengthen its long-term liquidity profile.

Based on Geron's current operating plan and assumptions regarding the timing of the potential approval and commercial launch of imetelstat in lower-risk MDS in the U.S., the company believes that its existing cash, cash equivalents, and current and noncurrent marketable securities, together with projected revenues from U.S. sales of imetelstat, if approved, potential proceeds from the exercise of outstanding warrants, and potential future drawdowns under the Loan Agreement, will be sufficient to fund its projected operating requirements into the second quarter of 2026.

Conclusion

Geron is poised for a potential breakthrough in the treatment of myelodysplastic syndromes with its investigational first-in-class telomerase inhibitor, imetelstat. The company's NDA for imetelstat in lower-risk MDS is currently under review by the FDA, with a PDUFA action date of June 16, 2024. Geron has also submitted an MAA in Europe for the same indication, with a potential approval and commercial launch in the EU expected in 2025.

The positive results from the IMerge Phase 3 trial, coupled with the overwhelming support from the ODAC, have positioned imetelstat as a highly differentiated treatment option for transfusion-dependent lower-risk MDS patients, particularly those with high unmet needs. Geron's commercial readiness efforts and strong financial position further bolster the company's prospects for a successful U.S. launch, if approved.

While Geron faces significant risks and challenges, including the potential for adverse events with imetelstat and the uncertainty of regulatory approvals, the company's laser-focus on imetelstat and its potential to transform the treatment landscape for myeloid hematologic malignancies make it a compelling investment opportunity for those willing to navigate the inherent risks.