Kairos Pharma Presents Preclinical Data on its Investigational Compounds KROS 101 and KROS 401 Further Supporting Both Compounds’ Potential as Therapeutics for Melanoma and Glioblastoma

On February 26, 2025 Kairos Pharma, Ltd. (NYSE American: KAPA), a clinical-stage biopharmaceutical company, reported that the company presented preclinical data on its investigational compounds KROS 101 and KROS 401 during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Immuno-Oncology (AACR IO) conference held in Los Angeles from February 23-26, 2025 (Press release, Kairos Pharma, FEB 26, 2025, View Source [SID1234650631]). The data highlighted positive preclinical outcomes with the Company’s glucocorticoid-induced tumor necrosis factor receptor (GITR) agonist KROS101 in melanoma and glioblastoma as well as its peptide inhibitor for macrophages KROS 401 in glioma animal models.

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In the presentation, titled "KROS 101: A Next Generation GITR agonist boosting anti-tumor T cell responses and reprogramming the tumor environment," study authors demonstrated that KROS significantly inhibited tumor growth in a preclinical melanoma model. The same team of scientists also showed that KROS 101 increased the proliferation of helper and cytotoxic T cells (CD4+ and CD8+), while decreasing T reg cell growth in a melanoma model. Further, T cells treated with KROS 101 showed cytotoxicity against glioblastoma cell lines and glioma cancer cells, which study authors, Admasu, et. al., concluded KROS 101 demonstrated potent anti-tumor activity compared to a previously used antibody against the GITR receptor TRX518 that was in clinical trials. Most importantly, the authors demonstrated KROS 101 but not TRX518 to prevent the exhaustion of T cells in the tumor.

The second presentation, titled "Targeting M2 macrophage polarization: The anti-tumor effects of IL-4/IL-13 blocking peptide and iron oxide nanoparticles," demonstrated the Company’s peptide inhibitor KROS 401 may effectively reprogram macrophages — types of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances – to inhibit tumor growth. The preclinical study demonstrated that KROS 401 exhibited an anti-tumor effect in glioma-bearing mice following a decrease in M2 macrophages, which are known to facilitate tumor growth.

Dr. John Yu, CEO of Kairos Pharma and co-inventor, commented, "We continue to receive validation of our preclinical data demonstrating our KROS platform’s development of anti-tumor therapies. KROS 101 addresses an Achille’s heel of all T cell immunotherapies and that is the development of exhaustion in anti-tumor T cells. KROS 101 appears to prevent the development of exhaustion by T cells enabling them to continue to kill tumor cells."

Dr. Ram Murali, VP of Research and Development stated, "KROS 401 is designed to reverse the M1 to M2 transition of macrophages in the tumor microenviroment. What this translates to is changing pro-tumor macrophages into anti-tumor macrophages. This leads to tumor-killing activity by both macrophages and T cells."

The American Association for Cancer Research (AACR) (Free AACR Whitepaper) Immuno-Oncology (AACR IO) encompasses the very best of basic, translational, and clinical research in immunology, inflammation, and immunotherapies for cancer, including immuno-oncology (IO) drugs, inflammatory modulators, vaccines, and cellular therapies. The cutting-edge AACR (Free AACR Whitepaper) IO 2025 program will appeal to a wide audience of basic scientists, translational researchers, clinical investigators, regulators, industry, investors, and lay press. A mix of keynote lectures, major symposia, spotlight sessions, educational sessions, special sessions, and poster sessions with exhibits will cover the spectrum of the IO field—including late-breaking clinical trials sessions highlighting new agents and IO combinations, and the results of practice-changing clinical trials.

Interim Phase 2 Results Suggest Zabadinostat Combination Improves Overall Survival in Advanced Liver Cancer

On February 26, 2025 IngenOx Therapeutics the Oxford-based biopharmaceutical company, reported positive interim results from its Phase 2 clinical trial investigating zabadinostat in combination with a PD-1 inhibitor for advanced hepatocellular carcinoma (HCC) (Press release, IngenOx Therapeutics, FEB 26, 2025, https://ingenox.com/interim-phase-2-results-suggest-zabadinostat-combination-improves-overall-survival-in-advanced-liver-cancer [SID1234650630]). The findings were presented at The Lancet Summit 2025 in Shanghai, China.

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Immune checkpoint inhibitors (ICIs) are increasingly used to treat advanced HCC. While some patients experience lasting responses, resistance to therapy is a common challenge. Collaborative preclinical research has shown that IngenOx’s zabadinostat reversed resistance to immune checkpoint inhibition in a clinically relevant orthotopic mouse HCC model (Tu et al., 2024). This study provided a strong scientific rationale for the clinical development of zabadinostat in combination with an ICI as a treatment for HCC patients who have become resistant to checkpoint blockade.

IngenOx is supporting a randomised Phase 2 clinical trial conducted by the Chinese University of Hong Kong (CUHK) to evaluate the safety and efficacy of zabadinostat combined with geptanolimab in ICI-resistant HCC patients (Experimental Arm), compared with a tyrosine kinase inhibitor such as lenvatinib or sorafenib (Control Arm). Geptanolimab is an ICI that targets the programmed cell death-1 (PD-1) receptor.

Interim results were presented by investigators at The Lancet Summit on Cancer Control in China, recently held in Shanghai (https://thelancetsummit.com/cancer-control-china/index.html). The results showed that the experimental combination with zabadinostat was associated with a higher disease stabilisation rate (61.5%; 95% CI 35–88%; n = 13) compared to the control group (46.2%; 95% CI 19–73%; n = 13). No difference in progression-free survival was observed between the groups. Median overall survival was 13.9 months (95% CI 8–14) in the Experimental Arm, compared to 9.3 months (95% CI 2–NR) in the Control Arm (HR 0.16, 95% CI 0.08–1.36, p = 0.12). These preliminary findings indicate that the combination therapy is well tolerated, associated with a higher disease control rate, and suggests a trend towards improved outcomes. The positive clinical results support the continued development of zabadinostat combinations for advanced cancer treatment.

David Kerr, CMO of IngenOx and Professor of Cancer Medicine at the University of Oxford commented:

"These promising clinical trial findings give us great confidence that we can recapitulate in patients the extraordinary results seen in mice models and deliver a telling blow to this awful disease. Our sophisticated trial design gives us the necessary clinical data to continue recruitment and stays true to our commitment to precision medicine as we interrogate the serial biopsies from our patients to discover potentially predictive biomarkers to further improve clinical outcomes."

Nick La Thangue, CEO of IngenOx and Professor of Cancer Biology at the University of Oxford commented:

"These encouraging early results continue to endorse zabadinostat as a potentially significant drug in resistant liver cancer. We are pleased to support this trial and look forward to continuing our important collaboration with colleagues in Hong Kong."

IN8bio to Present at the TD Cowen 45th Annual Health Care Conference

On February 26, 2025 IN8bio, Inc. (Nasdaq: INAB), a leading clinical-stage biopharmaceutical company focused on innovative gamma-delta T cell therapies, reported that William Ho, CEO and co-founder, will be presenting at the TD Cowen 45th Annual Health Care Conference on Monday, March 3, 2025, at 10:30 a.m. ET (Press release, In8bio, FEB 26, 2025, View Source [SID1234650629]).

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A live webcast and replay will be available under "Events and Presentations" in the News & Presentations section of the IN8bio website at View Source

Immunocore reports fourth quarter and full year 2024 financial results and provides a business update

On February 26, 2025 Immunocore Holdings plc (Nasdaq: IMCR) ("Immunocore" or the "Company"), a commercial-stage biotechnology company pioneering and delivering transformative immunomodulating medicines to radically improve outcomes for patients with cancer, infectious diseases and autoimmune diseases, reported its financial results for the fourth quarter and year ended December 31, 2024, and provided a business update (Press release, Immunocore, FEB 26, 2025, View Source [SID1234650628]).

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The Company has delivered 11 consecutive quarters of KIMMTRAK (tebentafusp) revenue growth with continued penetration in the U.S. and launches in 14 new territories ex-U.S., while executing on the product’s lifecycle management program through two Phase 3 trials (TEBE-AM and ATOM) in additional melanoma indications.

The Company further advanced its clinical pipeline, enrolling patients in its three Phase 3 trials, initiating patient dosing in its Phase 1 trial with IMC-P115C, its half-life extended candidate targeting PRAME, and administering the first dose of the first PIWIL1-targeted immunotherapy for gastrointestinal cancers.

Supported by a strong balance sheet, the Company also continued to innovate for sustainable growth, progressing two autoimmune candidates from its first-in-class, tissue-specific autoimmune platform towards clinical trial applications in 2025 and 2026.

"In 2024, we continued to grow KIMMTRAK sales, execute on our KIMMTRAK lifecycle management program, advance our deep clinical pipeline, and expand into autoimmune diseases, supported by a strong cash position and disciplined spending," said Bahija Jallal, CEO of Immunocore. "As we enter 2025, we continue enrolling patients in our three Phase 3 melanoma trials, pursuing additional opportunities in our PRAME franchise, and developing the next generation of transformative immunomodulating therapies. We have line of sight to a significant amount of data over the next 12-18 months, starting with the HIV data this quarter."

"In 2024 we launched KIMMTRAK in 14 countries and delivered 30% year-on-year net sales growth resulting in 11 successive quarters of continuous growth since launch," said Ralph Torbay, Head of Commercial. "In 2025, we expect incremental growth in metastatic uveal melanoma driven by further expansion into the U.S. community and additional launches. We will also continue to enroll patients in the Phase 3 TEBE-AM trial for advanced cutaneous melanoma, with data expected in 2026, and the Phase 3 ATOM trial for adjuvant uveal melanoma."

Full Year and Fourth Quarter 2024 Highlights (including post-period)

Financial Results

Total net product revenue (or ‘net sales’) arising from the sales of KIMMTRAK (tebentafusp) was $84.1 million in the fourth quarter of 2024, of which $63.8 million was generated in the United States, $17.8 million in Europe and $2.5 million in international regions. For the year ended December 31, 2024, the Company generated net sales of KIMMTRAK in the amount of $310.0 million, of which $226.7 million was in the United States, $73.2 million in Europe and $10.1 million in international regions.

Research & development (R&D) expenses for the year 2024 were $222.2 million, compared to $163.5 million for the year 2023. Selling, general and administrative (SG&A) expenses for the year 2024 were $155.8 million, compared to $144.5 million for the year 2023.

Net loss for the fourth quarter of 2024 was $23.8 million compared to a net loss of $19.7 million in the same period in 2023, and full year net loss for 2024 was $51.1 million compared to a full year net loss of $55.3 million in 2023.

The fourth quarter basic and diluted loss per share was $0.47 compared to $0.40 for the fourth quarter of 2023. Basic and diluted loss per share for the year 2024 was $1.02, compared to $1.13 for the year 2023.

Cash, cash equivalents and marketable securities at December 31, 2024, were $820.4 million. In November 2024, the Company repaid in full its existing Pharmakon loan of $50.0 million.

KIMMTRAK

The Company’s lead product, KIMMTRAK (tebentafusp), is approved in 39 countries and has been launched in 24 countries to date for HLA-A*02:01+ people with metastatic uveal melanoma (mUM). KIMMTRAK continues to be the standard of care in most markets where it is launched.

The Company sees three key growth areas for KIMMTRAK, including continued global expansion in mUM, the potential expansion into 2L+ advanced cutaneous melanoma (CM), and the potential expansion into adjuvant uveal melanoma.

Metastatic uveal melanoma

In 2024, KIMMTRAK was launched in 14 additional countries (including Australia, Spain, Poland, and the United Kingdom, excluding Scotland) for a total of 24 countries launched at the end of 2024.
The Company plans to expand access to KIMMTRAK through market share growth in key areas, early patient identification, and additional launches globally.
Second-line and later cutaneous melanoma

The Company is currently enrolling the TEBE-AM registrational Phase 3 trial and expects to complete enrollment in the first half of 2026.
The Phase 3 is enrolling three arms: tebentafusp monotherapy, tebentafusp in combination with pembrolizumab, and a control (investigator’s choice of therapy including options such as investigator’s choice of clinical trials, chemotherapy, or retreatment with anti-PD1 or BRAF therapy).
There is great unmet need in second and later-line cutaneous melanoma, with no therapy having shown an Overall Survival (OS) improvement post checkpoint inhibitors in a randomized clinical trial. The Company estimates that there is a potential to address up to 4,000 previously treated advanced CM patients.
Adjuvant uveal (or ocular) melanoma

In December 2024, the first patient was randomized in the Phase 3 Adjuvant Trial in Ocular Melanoma (ATOM), led by the European Organisation for Research and Treatment of Cancer (EORTC).
The Company estimates that the HLA-A*02:01 high risk adjuvant uveal melanoma patient population could be up to 1,200 patients.
PRAME portfolio

Brenetafusp is the Company’s lead PRAME-A02 ImmTAC bispecific candidate. Brenetafusp is being evaluated in combination with nivolumab in a Phase 3 registrational trial (PRISM-MEL-301) in patients with first-line advanced cutaneous melanoma, and in a Phase 1/2 clinical trial as monotherapy and in combination across multiple tumor types, including ovarian cancer and non-small cell lung cancer (NSCLC).

PRISM-MEL-301 – First PRAME Phase 3 clinical trial with brenetafusp in first-line advanced cutaneous melanoma

The Company randomized the first patient in the registrational Phase 3 clinical trial evaluating brenetafusp + nivolumab versus a control arm of either nivolumab or nivolumab + relatlimab for HLA-A*02:01 patients with first-line, advanced or metastatic cutaneous melanoma.
Selection of the go-forward dose by the independent data monitoring committee is expected in the second half of 2025.
Despite approved therapies, there remains a need for improved progression free survival and overall survival, and there is the potential to address an estimated 10,000 patients.
Phase 1/2 clinical trial of brenetafusp in multiple solid tumors

In 2024, the Company presented clinical data for the ongoing Phase 1/2 trial evaluating brenetafusp, as a monotherapy and in combination with standard of care. Brenetafusp monotherapy showed clinical activity (disease control rate, partial responses, and stable disease) and ctDNA molecular responses in late-line cutaneous melanoma (at ASCO (Free ASCO Whitepaper) 2024) and platinum-resistant, high grade serous ovarian cancer (at ESMO (Free ESMO Whitepaper) 2024).
Brenetafusp was safely combined with anti-PD1 and all tested chemotherapies in the trial.
The Company continues to evaluate brenetafusp in a Phase 1/2 trial in combination with non-platinum chemotherapies in platinum-resistant ovarian cancer (PROC) and with bevacizumab or with platinum chemotherapy in earlier lines of platinum-sensitive ovarian cancer (PSOC). In the same trial, the Company continues signal detection in metastatic non-small cell lung cancer cohorts, including brenetafusp in combination with docetaxel and with osimertinib in earlier-line NSCLC.
The Company estimates that, across all solid tumors, the annual number of patients worldwide who test positive for HLA-A*02:01 and can potentially benefit from this program is up to 150,000.
IMC-P115C (PRAME HLA-A02 Half-Life Extended) & IMC-T119C (PRAME HLA-A24)

In December 2024, the first dose was administered to a patient in the Phase 1 dose escalation trial, in multiple solid tumors, with IMC-P115C.
IMC-P115C is the Company’s first half-life extended ImmTAC therapy – targeting the same PRAME peptide and with the same CD3 effector and TCR specificity as brenetafusp. It is designed to improve patient convenience by reducing the frequency of treatment administration.
The Company submitted a clinical trial application (CTA) to regulatory authorities for IMC-T119C (targeting PRAME HLA-A24), in December 2024.
IMC-R117C (PIWIL1) for colorectal and other gastrointestinal cancers

In December 2024, the first patient was dosed with IMC-R117C (targeting PIWIL1) in the Phase 1/2 dose escalation trial. PIWIL1 is believed to play a role in tumor progression and is expressed across a range of tumors, including colorectal cancer.
The trial evaluates IMC-R117C in HLA-A*02:01-positive patients with advanced solid tumors, including colorectal cancer, as a single agent and in combination with standards of care.
Enrolling ImmTAV candidates for a functional cure in infectious diseases

The Company’s bispecific TCR technology platform has potential to offer a new approach for the treatment of chronic infections and aims to eliminate evidence of remaining virus in circulation after a person stops taking medication – known as a ‘functional cure’. Two investigational candidates are in Phase 1 clinical trials for people living with human immunodeficiency virus (HIV) and people with chronic hepatitis B infection (HBV).

Phase 1 trial of IMC-M113V (Gag-A02) for people living with HIV

The Company continues to enroll people living with HIV (PLWH) in the multiple ascending dose (MAD) part of the Phase 1 clinical trial with IMC-M113V and will present data from the initial three cohorts during the first quarter of 2025.
The trial aims to identify a safe and tolerable dosing schedule, test whether IMC-M113V could lead to reduction in the viral reservoir and, after stopping all therapies (antiretroviral therapies and IMC-M113V), delay or prevent HIV rebound (known as functional cure). A biologically active dose has been reached, and the Company is enrolling more PLWH to further characterize anti-viral activity and explore higher doses.
Phase 1 trial of IMC-I109V (Envelope-A02) for people living with HBV

The Company completed the single ascending dose (SAD) portion of the Phase 1 trial with IMC-I109V for people living with hepatitis B virus (HBV) and plans to present this data in the second half of 2025.
Tissue-specific down modulation of the immune system for autoimmune diseases

The key differentiator of the ImmTAAI platform is tissue-specific, down modulation of the immune system, as the candidates suppress pathogenic T cells via PD1 receptor agonism only when tethered to the target tissue.

IMC-S118AI for type 1 diabetes

The Company plans to file a CTA or investigational new drug application (IND) for IMC-S118AI (PPI x PD1) in the second half of 2025.
IMC-S118AI is targeted specifically to the pancreatic beta-cell and intended as a disease-modifying treatment in type 1 diabetes. IMC-S118AI recognizes a peptide from pre-pro-insulin protein that is presented by HLA-A02 on beta cells and has a PD1 agonist effector arm.
IMC-U120AI initially for atopic dermatitis – first universal program

IMC-U120AI (CD1a x PD1) is a CD1a-tethered PD1 agonist ImmTAAI therapy. It is Immunocore’s first non-HLA-restricted program (i.e. universal for all populations).
The Company plans to file a CTA/IND for IMC-U120AI in 2026, initially for a Phase 1 dose escalation trial in atopic dermatitis.
CD1a is an HLA-like protein that is expressed on skin and mucosal antigen presenting cells, such as Langerhans cells. Both CD1a and Langerhans cells play an important role in triggering allergic inflammation in atopic dermatitis and potentially other immune diseases.
IMC-U120AI has a dual mechanism of action in that it will block CD1a (which presents lipids) from activating CD1a-specific T cells and will prevent HLA Class I/II (which presents peptides) from activating T cells via PD1 agonism on the T cell.
Corporate update

In February, Dr. William Pao was appointed as a non-executive member of the Company’s Board of Directors. William is the co-founder and Chief Executive Officer of Revelio Therapeutics, Inc. Prior to Revelio, Dr. Pao held executive leadership positions in early- and late-stage R&D at F. Hoffmann-La Roche AG and Pfizer respectively. He is a member of the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s board of directors.

Financial Results

Basic and diluted loss per share was $0.47 and $1.02 for the quarter and year ended December 31, 2024, respectively, as compared to a basic and diluted loss per share of $0.40 and $1.13, respectively, for the same periods in 2023. Net loss for the quarter and year ended December 31, 2024, was $23.8 million and $51.1 million, respectively, as compared to $19.7 million and $55.3 million, respectively, for the same periods in 2023.

For the fourth quarter and year ended December 31, 2024, the Company generated net sales of $84.1 million and $310.0 million, respectively, arising from the sale of KIMMTRAK, of which $63.8 million and $226.7 million, respectively was in the United States, $17.8 million and $73.2 million, respectively, was in Europe, and $2.5 million and $10.1 million, respectively, was in the international regions. The increase in net sales was due primarily to increased volume in the United States and global country expansion, as the Company continues its commercialization efforts.

For the fourth quarter and year ended December 31, 2024, Immunocore’s R&D expenses were $60.9 million and $222.2 million, respectively as compared to $45.6 million and $163.5 million for the quarter and year ended December 31, 2023. These increases were primarily driven by expenses incurred for the Company’s PRAME programs as a result of the initiation of our registrational Phase 3 PRISM-MEL-301 clinical trial, scale-up of manufacturing and an increase in the number of patients in combination expansions in the brenetafusp Phase 1/2 clinical trial. R&D expenses incurred for the tebentafusp programs also increased due to the TEBE-AM and ATOM Phase 3 clinical trials. The Company expects R&D expenses to increase in 2025 as the Company further advances clinical and preclinical pipeline candidates.

For the quarter and year ended December 31, 2024, the Company’s SG&A expenses were $42.3 million and $155.8 million, respectively, compared to $41.4 million and $144.5 million for the quarter and year ended December 31, 2023. These increases were primarily related to increases in the number of employees engaged in business support functions to support our growing pipeline and global commercial expansion, and in investments in patient support initiatives, information technology and facilities costs. The Company expects SG&A expenses to be mostly consistent with Q4 2024 expense levels over the course of 2025.

Cash, cash equivalents and marketable securities at December 31, 2024, were $820.4 million. In November 2024, the Company repaid in full its existing Pharmakon loan of $50.0 million.

See the Company’s Annual Report on Form 10-K filed today with the SEC for more information.

Audio Webcast

Immunocore will host a conference call today, February 26, 2025, at 8:00 A.M. ET / 1:00 PM GMT, to discuss the fourth quarter and full year 2024 financial results and provide a business update. The call will also be available via webcast by visiting the Events & Presentations section on Immunocore’s website. A replay of this webcast will be available for 30 days.

Conference Call Details:
Domestic (toll-free): 877-405-1239
International (toll): +1 201-389-0851

Upcoming Investor Conferences

B. Riley Securities Precision Oncology & Radiopharma Conference
Friday, February 28, 2025, at 10:00 a.m. ET

Geron Corporation Reports Fourth Quarter and Full Year 2024 Financial Results and Recent Business Highlights

On February 26, 2025 Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, reported financial results for the fourth quarter and full year 2024 and recent business highlights (Press release, Geron, FEB 26, 2025, View Source [SID1234650627]).

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"2024 was a terrific year for Geron and for RYTELO, our first-in-class telomerase inhibitor, which we believe represents a highly differentiated treatment with blockbuster potential in the high unmet need, lower-risk MDS patient population. We also continued to progress our development efforts in relapsed/refractory myelofibrosis, which could potentially double our commercial opportunity if our IMpactMF Phase 3 trial reads out positively and we are approved in this indication. From a financial perspective, we ended the year with a strong cash position, and Q3 and Q4 revenues exceeded our expectations. Heading into 2025, we are excited by the strategic and leadership changes we put in place early in the launch, which we believe will position us to increase our revenue growth trajectory and more fully capture the significant commercial opportunity over the next several quarters," said John A. Scarlett, M.D., Geron’s Chairman and Chief Executive Officer.

Recent Business Highlights

Continued execution on U.S. commercial launch, with net product revenue for RYTELO (imetelstat) of $47.5 million in the fourth quarter of 2024 and $76.5 million since launch at the end of June 2024, following approval by the U.S. Food and Drug Administration (FDA).
Received positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) in December 2024 recommending approval of RYTELO for the treatment of certain adult patients with transfusion-dependent anemia due to lower-risk MDS. Subject to receiving regulatory approval, which is expected in the first half of 2025, Geron is preparing to commercialize RYTELO in select EU countries in 2026.
Achieved approximately 80% enrollment in the Phase 3 IMpactMF trial evaluating imetelstat in patients with relapsed/refractory myelofibrosis (R/R MF). Based on our current planning assumptions for enrollment and event (death) rates in the trial, we now expect the interim analysis for overall survival may occur in the second half of 2026 (when approximately 35% of planned enrolled patients have died) and the final analysis may occur in the second half of 2028 (when approximately 50% of planned enrolled patients have died).
Presented new data at the 66thAmerican Society for Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2024, including analyses of IMerge Phase 3 data suggesting clinical activity of imetelstat in patients with lower-risk MDS regardless of type or number of prior therapies and Phase 1 findings from IMproveMF suggesting tolerability of imetelstat in combination with ruxolitinib as a potential frontline therapy in patients with MF.
Fourth Quarter 2024 Financial Results

As of December 31, 2024, we had approximately $502.9 million in cash, cash equivalents, restricted cash and marketable securities.

Net Loss

For the three and twelve months ended December 31, 2024, the Company reported a net loss of $25.4 million, or $0.04 per share, and $174.6 million, or $0.27 per share, respectively, compared to $52.0 million, or $0.09 per share, and $184.1 million, or $0.32 per share, respectively, for the three and twelve months ended December 31, 2023.

Revenues

Total product revenue, net for the three and twelve months ended December 31, 2024, was $47.5 million and $76.5 million, respectively. There was no product revenue in the prior year periods, given that RYTELO was approved by the FDA in June 2024.

Total net revenue for the three and twelve months ended December 31, 2024, was $47.5 million and $77.0 million, respectively, compared to $23,000 and $237,000 for the same periods in 2023. Total net revenue includes license fees and royalties in addition to any product revenue, net. The increase in revenue is due to product revenue from U.S. sales of RYTELO, which was approved by the FDA in June 2024.

Operating Expenses

Total operating expenses for the three and twelve months ended December 31, 2024, were $67.6 million and $250.7 million, respectively, compared to $54.3 million and $194.2 million for the same periods in 2023.

Cost of goods sold was approximately $783,000 and $1.3 million for the three and twelve months ended December 31, 2024, respectively, which consisted of costs to manufacture and distribute RYTELO, compared to nil in the prior year periods.

Research and development expenses for the three and twelve months ended December 31, 2024, were $23.4 million and $103.7 million, respectively, and $32.9 million and $125.0 million, for the same periods in 2023. The decrease is primarily due to manufacturing and quality costs that were capitalized in the current period due to FDA approval of RYTELO, compared to being expensed in the prior period. The decrease is partially offset by an increase in labor costs due to higher headcount and incentive and stock-based compensation expense recognized due to the vesting of performance-based stock options upon FDA approval of RYTELO.

Selling, general and administrative expenses for the three and twelve months ended December 31, 2024, were $43.4 million, and $145.7 million, respectively, and $21.4 million and $69.1 million for the same periods in 2023. The increase in general and administrative expenses in 2024 as compared to 2023 primarily reflects higher personnel-related expenses related to increased headcount to support commercial launch of RYTELO in the U.S. and stock-based compensation expense recognized upon FDA approval of RYTELO due to the vesting of performance-based stock options.

Interest income was $5.2 million and $19.6 million for the three and twelve months ended December 31, 2024, respectively, compared to $4.6 million and $18.2 million for the same periods in 2023. The increase in interest income in 2024 compared to 2023 primarily reflects a larger marketable securities portfolio due to the receipt of net cash proceeds from the underwritten offering completed in March 2024, as well as higher yields from marketable securities purchases. Interest earned in future periods will depend on the size of our marketable securities portfolio and prevailing interest rates.

Interest expense was $8.7 million and $18.5 million for the three and twelve months ended December 31, 2024, respectively, compared to $2.3 million and $8.3 million or the same periods in 2023. The increase in interest expense primarily reflects $5.3 million in non-cash interest expense related to our agreement with Royalty Pharma and an increased principal debt balance under the Pharmakon loan agreement and the Hercules loan agreement which was repaid in the fourth quarter of 2024. Interest expense reflects interest owed under the loan agreements, interest expense recognized under the Royalty Pharma agreement, as well as amortization of associated debt issuance costs and debt discounts using the effective interest method and accrual for an end of term charge.

Loss on extinguishment of debt

We recorded a loss on the extinguishment of debt of $1.7 million for the twelve months ended December 31, 2024. The loss is related to the settlement of debt outstanding under the terminated Hercules loan agreement.

2025 Financial Guidance

For fiscal year 2025, we expect total operating expenses to be in the range of approximately $270 million to $285 million, which includes non-cash items such as stock-based compensation expense, amortization of debt discounts and issuance costs, and depreciation and amortization.

We expect to reach profitability without additional financing if our current internal sales and operating expense expectations are met. Based on our current operating plans and assumptions, we believe that our existing cash, cash equivalents, and marketable securities, together with anticipated net revenues from U.S. sales of RYTELO, will be sufficient to fund our projected operating requirements for the foreseeable future.

Conference Call

Geron will host a conference call at 8:00 a.m. ET on Wednesday, February 26, 2024, to discuss business updates and fourth quarter and full year 2024 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

About RYTELO (imetelstat)

RYTELO (imetelstat) is an FDA-approved oligonucleotide telomerase inhibitor for the treatment of adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). It is indicated to be administered as an intravenous infusion over two hours every four weeks.

A marketing authorization application for RYTELO is under review by the European Commission as a monotherapy treatment for adult patients with transfusion-dependent anemia due to very low, low or intermediate risk myelodysplastic syndromes (MDS) without an isolated deletion 5q cytogenetic (non-del 5q) abnormality and who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy.

RYTELO is a first-in-class treatment that works by inhibiting telomerase enzymatic activity. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In LR-MDS, abnormal bone marrow cells often express the enzyme telomerase, which rebuilds those telomeres, allowing for uncontrolled cell division. Developed and exclusively owned by Geron, RYTELO is the first and only telomerase inhibitor approved by the U.S. Food and Drug Administration.