On April 20, 2026 Enara Bio, a pioneer in Dark Antigen discovery and bispecific T cell engager (TCE) innovation, reported the presentation of new preclinical data for ENA101, its first‑in‑class bispecific T cell engager (TCE), delivered today in an oral session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2026.

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ENA101 targets DARKFOX, a novel, cancer‑specific Dark Antigen encoded by a previously undiscovered alternative open reading frame (alt‑ORF) within FOXM1. DARKFOX was discovered and validated using Enara’s proprietary EDAPT platform and represents a new class of highly tumor‑specific targets derived from the dark proteome.

"ENA101 exemplifies the power of uncovering antigens within the dark proteome to overcome long-standing challenges in solid tumor immunotherapy," said Dr. Joe Dukes, Chief Scientific Officer of Enara Bio. "The data presented today at AACR (Free AACR Whitepaper) demonstrate that DARKFOX is a compelling cancer specific target and that ENA101 exhibits the potency, specificity and druglike profile required to advance a best-in-class T cell engager toward the clinic."

The oral presentation, titled "ENA101: A First‑in‑Class Bispecific T Cell Engager Targeting a DARKFOX Peptide Presented by Solid Tumors," was delivered by Dr. Joe Dukes in the Advances in Therapeutic Antibodies session
(Abstract #4052). The presentation highlighted the discovery of DARKFOX, the engineering of ENA101, and the comprehensive preclinical dataset supporting its advancement into clinical development.

Enara Bio is currently advancing ENA101 through IND-enabling studies to support IND filing in 2H’2026.

The abstract is available in Proceedings of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2026.

About ENA101
ENA101 is a first‑in‑class bispecific T cell engager developed using Enara Bio’s proprietary EnTiCE platform. It incorporates a high‑affinity TCR‑mimic binder targeting the DARKFOX‑A3 peptide, a clinically validated anti‑CD3 arm, and an Fc‑based architecture for half‑life extension, to enable potent, selective and durable anti‑tumor immune responses.

(Press release, Enara Bio, APR 20, 2026, View Source [SID1234664592])

On April 20, 2026 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on its Phase III clinical trial, FLAMINGO-01, which is evaluating Fast Track designated GLSI-100, an immunotherapy to prevent breast cancer recurrences, reported the published abstract and poster from the AACR (Free AACR Whitepaper) Meeting 2026.

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The abstract is shown below and the poster being presented today can be seen and downloaded at the bottom of Phase III clinical trial tab on the Company’s website here.

This is the first abstract and poster presented jointly with the Steering Committee of FLAMINGO-01 with statistically significant delayed-type-hypersensitivity (DTH) immune response data, with subgroup analysis by the most prevalent HLA types.
In the non-HLA-A*02 open label arm where all patients (n=247) were treated with GLSI-100, immune responses to GP2 were measured at baseline and over time using skin tests and other methods. The other methods will be presented at a future conference.
A DTH reaction (redness and/or induration) was used to assess in vivo immune responses in patients. The DTH orthogonal mean was also measured 48-72 hours after injection but is not reported here.
In this preliminary data analysis, there was a significant increase in percentage of patients experiencing a DTH reaction (redness) in month 4 or month 6 compared to baseline. There were 191 patients with both baseline and month 4 or 6 assessments.
The frequency of DTH reactions increased by approximately 4x (290%) in the total open-label non-HLA-A*02 population, increasing from 5.2% of the patients experiencing a DTH reaction at baseline, prior to any GLSI-100 administration, to 20.4% of the patients experiencing a DTH reaction in month 4 or month 6 (McNemar, p < 0.001).
As reported in Table 1 of the poster, each HLA-A type exhibited more frequent immune reactivity after treatment with GLSI-100 than at baseline with frequency increasing from 100% to 700%.
Baseline DTH reaction prior to any treatment suggests that GP2 may be a natural antigen and that GP2 specific T cells may exist in some patients prior to any treatment with GLSI-100. Baseline immune response to GP2 prior to any vaccination with GP2 was also observed in the Phase IIb trial and is being observed in the blinded randomized arms of FLAMINGO-01, where HLA-A*02 only patients are being vaccinated.
Mechanism of Action: A positive immune response is an indicator that the immune system has been activated against recurring cancer cells, potentially leading to the prevention of metastatic breast cancer. The Company previously announced that in the non-HLA-A*02 arm, a preliminary analysis of recurrence rates after the Primary Immunization Series (PIS) is completed shows an approximately 70-80% reduction in recurrence rate. Thus, the immune response data is supporting the mechanism of action that reduces recurrences and prevents metastatic breast cancer.
This statistically significant non-HLA-A*02 open label arm immune response data is trending similarly to the immune response data in the HLA-A*02 patients in the Phase IIb study and the HLA-A*02 arms of FLAMINGO-01. The study is ongoing and data collection and cleaning continue, while some patients may still be in their PIS vaccination phase, so final results may vary.
A 1% per year recurrence rate is so low that the number of recurrence events is too few to correlate a negative or lack of immune response to recurrence. The same constraint existed with the Phase IIb data which has a similarly low recurrence rate per year. While DTH immune response may be valuable at an aggregate level looking at whole patient populations, the recurrence rate is too low to validate any immune response measure as a biomarker for individual patient treatment decisions. It is also likely that some responding patients may not exhibit any immune response but still could be protected by GLSI-100 vaccination, thus helping to preserve the blind on the randomized arms of FLAMINGO-01.

The immune response abstract and poster conclusion: The statistically significant increase in the incidence of DTH reactions over time found in this preliminary analysis of GLSI-100 treated non-HLA-A*02 patients shows that GLSI-100 treatment should not be limited to HLA-A*02 patients. Patients treated with GLSI-100 were increasingly able to mount an immune response to GP2 as evidenced in this preliminary data. Future investigations may explore the use of immune responses to assess correlation of DTH to ISRs, immunogenicity of GLSI-100 by specific HLA type, timing of boosters to sustain immunity, clinical site performance, and the discontinuation of treatment for non-responders.

In addition, the second poster describing the Phase III trial design, which is being presented on Tuesday, April 21, can be downloaded and seen on the website using the same link. This poster provides an update that over 1,300 patients have been screened to date in FLAMINGO-01. The new protocol amendment, which is still under regulatory review in certain countries, is not discussed.

CEO Snehal Patel commented, "This new immune response data further supports the combination of HLA-A*02 and non-HLA-A*02 patients in the same randomized arms. In the US, the FDA recently reviewed such protocol changes and the many non-HLA-A*02 patients on waiting lists that were previously screened are now being enrolled. The screen rate continues to be encouraging, reflecting the high patient interest in the study as we have now screened over 1,300 patients. The Company will have the option to pursue approval for both HLA-A*02 and non-HLA-A*02 patients together using the increased statistical power of a combined analysis of the two patient groups or to pursue subgroups based on planned multiple interim analyses."

The abstract from today’s immune response data and the members of the Steering Committee follow:

Abstract Number: CT138 – Poster Section 52 on April 20, 2026, 2-5pm PT

Abstract Title: Preliminary delayed-type-hypersensitivity immune response results from open-label arm of on-going Phase III study to evaluate the efficacy and safety of GLSI-100 (GP2 + GM-CSF) in breast cancer patients with residual disease or high-risk PCR after both neo-adjuvant and postoperative adjuvant anti-HER2 therapy, Flamingo-01

Snehal S. Patel1, Jaye Thompson1, F. Joseph Daugherty1, Francois-Clement Bidard2, William J. Gradishar3, Marcus Schmidt4, Miguel Martin5, Joyce A. O’Shaughnessy6, Hope S. Rugo7, Cesar A. Santa-Maria8, Laura M. Spring9, Mothaffar F. Rimawi10

1Greenwich LifeSciences, Stafford, TX,2Institut Curie, Paris, France,3Northwestern University, Chicago, IL,4University Medical Center Mainz, Mainz, Germany,5GEICAM, Madrid, Spain,6Sarah Cannon Research Institute, Dallas, TX,7City of Hope Comprehensive Cancer Center, Duarte, CA,8Johns Hopkins University, Baltimore, MD,9Massachusetts General Hospital, Boston, MA,10Lester and Sue Smith Breast Center, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX

Background: This Phase III trial is a prospective, randomized, double-blinded, multi-center study (NCT05232916) in HLA-A*02 patients at approximately 140 sites in the US and Europe. A third non-randomized arm of approximately 250 non-HLA-A*02 patients is now fully enrolled and preliminary immune response data is presented below. GP2 is a biologic nine amino acid peptide of the HER2/neu protein delivered in combination with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) that stimulates an immune response targeting HER2/neu expressing cancers, the combination known as GLSI-100.

Methods: After standard of care neoadjuvant and adjuvant therapy, 6 intradermal injections of GLSI-100 will be administered over the first 6 months and 5 subsequent boosters will be administered over the next 2.5 years. The participant duration of the trial will be 3 years treatment plus 1 additional year follow-up. Immune responses to GP2 were measured over time using delayed-type-hypersensitivity (DTH) skin tests and injection site reactions (ISRs). The patient population is defined by these key eligibility criteria: 1) HER2/neu positive and HLA, 2) Residual disease or High risk pCR (Stage III at presentation) post neo-adjuvant therapy, 3) Exclude Stage IV, and 4) Completed at least 90% of planned trastuzumab-based therapy.

Results: All patients (n=247) were vaccinated with GLSI-100 and continue in treatment and follow-up. A DTH reaction (redness) was used to assess in vivo immune responses in patients. The DTH orthogonal mean was measured 48-72 hours after injection. In this preliminary data analysis, there was a significant increase in percentage of subjects experiencing a DTH reaction in month 4 or month 6 compared to baseline. The frequency of DTH reactions increased by approximately 4x from 5.2% of the patients experiencing a DTH reaction at baseline, prior to any GLSI-100 administration, to 20.4% of the patients experiencing a DTH reaction in month 4 or month 6 (McNemar, p < 0.001). The study is ongoing and data collection and cleaning continue so final results may vary.

Conclusions: The increase in the incidence of DTH reactions over time found in this preliminary analysis of GLSI-100 treated non-HLA-A*02 patients shows that GLSI-100 treatment should not be limited to the HLA-A*02 genotype. Subjects treated with GLSI-100 were increasingly able to mount an immune response to GP2 as evidenced in this preliminary data. Future investigations may explore the use of immune responses to assess: correlation of DTH to ISRs, immunogenicity of GLSI-100 by specific HLA type, timing of boosters to sustain immunity, clinical site performance, and the discontinuation of treatment for non-responders.

The Steering Committee authoring abstract CT138 is comprised of the following experts in the field of breast cancer oncology representing prominent teaching hospitals in the US and 4 of the largest breast oncology networks in the US, Germany, France, and Spain:

Dr. Mothaffar F. Rimawi – Professor of Medicine at the Baylor College of Medicine and Executive Medical Director and Co-Leader, Breast Cancer Program of the Dan L Duncan Comprehensive Cancer Center
Dr. Francois-Clement Bidard – Professor of Medical Oncology, UVSQ/Paris Saclay University, Head of Breast Cancer Group, Institut Curie, Vice-Chair of the French Breast Cancer research group UCBG (Unicancer)
Dr. William J. Gradishar – Professor of Medicine at the Feinberg School of Medicine at Northwestern University, Chief of Hematology and Oncology in the Department of Medicine, and Betsy Bramsen Professor of Breast Oncology
Dr. Sibylle Loibl – Professor (apl) Goethe University Frankfurt/M, Clinical Consultant Centre for Haematology and Oncology/Bethanien Frankfurt/M, CEO of GBG Forschungs GmbH & Chair of the German Breast Group (GBG)
Dr. Miguel Martin – Professor of Medicine, Head, Medical Oncology Service, Gregorio Marañón General University Hospital, Complutense University, Madrid, CEO of GEICAM
Dr. Joyce A. O’Shaughnessy – Celebrating Women Chair in Breast Cancer, Baylor University Medical Center and Chair, Breast Cancer Program, Texas Oncology, US Oncology, Dallas, Texas
Dr. Hope S. Rugo – Director, Women’s Cancers Program, Division Chief, Breast Medical Oncology, Professor, Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Professor Emeritus, University of California, San Francisco
Dr. Cesar A. Santa-Maria – Associate Professor of Oncology, Breast and Gynecological Malignancies Group, Director of Breast Cancer Trials, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Dr. Laura M. Spring – Assistant Professor, Medicine, Harvard Medical School, Attending Physician, Medical Oncology, Massachusetts General Hospital
About the AACR (Free AACR Whitepaper) Annual Meeting 2026

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About FLAMINGO-01 Open Label Phase III Data
More than 1,000 patients have been screened with a current screen rate of approximately 800 patients per year. The 250 patient non-HLA-A*02 arm is now fully enrolled, where all patients received GLSI-100, which is 5 times more treated patients and recurrence rate data than the approximately 50 patients treated in the Phase IIb trial. The Primary Immunization Series (PIS), which includes the first 6 GLSI-100 injections over the first 6 months and is required to reach peak protection, is followed by 5 booster injections given every 6 months to prolong the immune response, thereby providing longer-term protection.

In the non-HLA-A*02 arm, a preliminary analysis of recurrence rates after the PIS is completed shows an approximately 70-80% reduction in recurrence rate.
This observation is trending similarly to the Phase IIb trial results and hazard ratio where HLA-A*02 patients were treated and where breast cancer recurrences were reduced up to 80% compared to a 20-50% reduction in recurrence rate by other approved products.
The immune response at baseline prior to any GLSI-100 treatment, the increasing immune response during the PIS, and the safety profile of non-HLA-A*02 patients is trending similarly to the HLA-A*02 arms of FLAMINGO-01 and to the Phase IIb study.

Analysis of the open label data from FLAMINGO-01 has been conducted in a manner that maintains the study blind. The open label recurrence rate, immune response, and safety data is based on the patients enrolled to date in FLAMINGO-01 and the data provided by the clinical sites so far, which is not completed or fully reviewed, and is thus preliminary. While comparing any preliminary FLAMINGO-01 data to the Phase IIb clinical trial data may be possible, these preliminary results are not a prediction of future results, and the results at the end of the study may differ.

About GLSI-100 Phase IIb Study

In the prospective, randomized, single-blinded, placebo-controlled, multi-center (16 sites led by MD Anderson Cancer Center) Phase IIb clinical trial of HLA-A*02 breast cancer patients, 46 HER2/neu 3+ over-expressor patients were treated with GLSI-100, and 50 placebo patients were treated with GM-CSF alone. After 5 years of follow-up, there was an 80% or greater reduction in cancer recurrences in the HER2/neu 3+ patients who were treated with GLSI-100, followed, and remained disease free over the first 6 months, which we believe is the time required to reach peak immunity and thus maximum efficacy and protection. The Phase IIb results can be summarized as follows:

80% or greater reduction in metastatic breast cancer recurrence rate over 5 years of follow-up with a peak immune response at 6 months and well-tolerated safety profile.
The PIS elicited a potent immune response as measured by local skin tests and immunological assays.
About FLAMINGO-01 and GLSI-100

FLAMINGO-01 (NCT05232916) is a Phase III clinical trial designed to evaluate the safety and efficacy of Fast Track designated GLSI-100 (GP2 + GM-CSF) in HER2 positive breast cancer patients who had residual disease or high-risk pathologic complete response at surgery and who have completed both neoadjuvant and postoperative adjuvant trastuzumab based treatment. The trial is led by Baylor College of Medicine and currently includes US and European clinical sites from university-based hospitals and academic and cooperative networks with plans to open up to 150 sites globally. In the double-blinded arms of the Phase III trial, approximately 500 HLA-A*02 patients are planned to be randomized to GLSI-100 or placebo, and up to 250 patients of other HLA types are planned to be treated with GLSI-100 in a third arm. The trial has been designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater.

For more information on FLAMINGO-01, please visit the Company’s website here and clinicaltrials.gov here. Contact information and an interactive map of the majority of participating clinical sites can be viewed under the "Contacts and Locations" section. Please note that the interactive map is not viewable on mobile screens. Related questions and participation interest can be emailed to: [email protected]

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 300,000 new breast cancer patients and 4 million breast cancer survivors. HER2 (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.

(Press release, Greenwich LifeSciences, APR 20, 2026, View Source [SID1234664540])

On April 20, 2026 Lantern Pharma Inc. (NASDAQ: LTRN), an AI-driven precision oncology company, reported it has scheduled a Type C meeting with the U.S. Food and Drug Administration (FDA) for mid-May 2026 to seek feedback on proposed protocol amendments to its ongoing Phase 2 HARMONIC clinical trial evaluating LP-300. The amendments are grounded in emerging clinical data demonstrating a meaningful and consistent progression-free survival signal in patients with EGFR Exon 21 L858R-mutant non-small cell lung cancer (NSCLC) who have progressed following any TKI-based treatment (including osimertinib) — a population carrying a particularly poor prognosis and limited remaining therapeutic options. Lantern is seeking the FDA’s scientific guidance to sharpen the trial design around the patients most likely to benefit, and to pursue the most rigorous and efficient development path possible.

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Emerging Clinical Evidence: A Consistent and Coherent Signal

Preliminary clinical data from the HARMONIC trial, with a data cutoff of April 13, 2026, have revealed a differentiated and consistent progression-free survival profile for LP-300 in patients harboring the EGFR Exon 21 L858R mutation — accounting for approximately 40% of all EGFR-mutant NSCLC cases globally, and a subgroup with a notably inferior prognosis following frontline TKI (including osimertinib) therapy compared with Exon 19 deletion patients. Among the 16 L858R-mutant patients enrolled in HARMONIC, LP-300 in combination with carboplatin and pemetrexed demonstrated:

8.3 mo

mPFS — L858R Patients

n=16 | 95% CI: 6.2–NC

86% / 43%

Clinical Benefit Rate / ORR

Safety Lead-In Cohort (US)

HR 0.37

L858R vs. Non-L858R

95% CI: 0.15–0.89

~$4B+

Annual Market Opportunity

L858R-enriched never-smoker NSCLC

These outcomes were observed in patients who had already progressed on tyrosine kinase inhibitor (TKI) therapy — a setting where prognosis is particularly challenging and where treatment tolerability is a critical consideration. The upper confidence interval for mPFS (median progression-free survival) for the L858R patient group remains not calculable at the time of analysis, suggesting that a meaningful proportion of patients may be achieving disease control that extends substantially beyond the reported median. The Hazard Ratio (HR) observations to date for the L858R patient group are also encouraging.

Independent Statistical Signal: Multivariable Analysis

To assess whether the emerging L858R efficacy signal might be explained by other patient characteristics, a multivariable Cox regression analysis was conducted incorporating race, gender, and TP53 mutation status. The L858R mutation remained a statistically significant independent predictor of progression-free survival across all models tested:

After adjusting for race and gender: HR 0.36 (95% CI: 0.15–0.90, p=0.028) — no significant associations were observed for race or gender alone
After incorporating TP53 mutation status: HR 0.23 (95% CI: 0.06–0.91, p=0.036) — L858R effect remained significant
These analyses are exploratory and based on a small patient cohort. Lantern plans to support these findings with additional data from the ongoing HARMONIC trial as enrollment and patient monitoring continues.

Durable Clinical Benefit: Depth and Persistence of Response

Beyond the overall L858R progression-free survival signal, exploratory analyses from the HARMONIC trial reveal several findings that further support the depth and durability of LP-300’s activity in this patient population.

Dose-Duration Signal: More Cycles, Better Outcomes

Among L858R patients in HARMONIC, those who completed 6 doses or cycles of LP-300 demonstrated a higher median PFS than the overall L858R cohort:

L858R patients completing 6 cycles of LP-300 showed a mPFS = 8.9 months (n=9, 3 patients had not yet progressed at the time of analysis)
Comparable safety profiles were observed across patients receiving 4 or 6 cycles, with no evidence of increased adverse events with longer treatment duration
This dose-duration trend is consistent with LP-300’s kinase inhibitory mechanism of action and provides supporting scientific rationale for the proposed extension of maximum treatment cycles from 6 to 8. These data are exploratory and based on small patient numbers; Lantern expects to further characterize this relationship as the trial continues.

Heavily Pretreated Patients: A Notable Signal in a Difficult Setting

Among the subset of L858R patients who had received two prior lines of systemic therapy — a particularly challenging population to treat — an encouraging preliminary signal was observed:

L858R patients with 2 prior systemic therapies: mPFS = 13.5 months (n=5; 3 patients had not yet progressed at the time of analysis)
One patient in this cohort achieved a durable complete response in target lesions, with survival continuing beyond two years. Notably, this patient’s response deepened over time, progressing from an initial partial response to a confirmed complete response — a pattern consistent with an ongoing and evolving treatment effect.
These data represent a very small patient subset and should be interpreted with appropriate caution. Individual patient outcomes may not be representative of the broader population. These findings are hypothesis-generating and will require confirmation in larger cohorts.

Why L858R — and Why Does It Matter?

The Scientific Rationale: Why LP-300 May Be Uniquely Suited to L858R

The L858R substitution replaces leucine — a hydrophobic amino acid — with positively charged arginine, disrupting the hydrophobic interactions that normally stabilize the EGFR kinase domain in its inactive conformation. The result is a receptor that preferentially adopts the active state. Critically, however, unlike Exon 19 deletion mutants — where the shortened αC-helix locks the receptor into a stable, monomer-capable active orientation — L858R tumors still require receptor dimerization to complete oncogenic activation and transformation.

This significant mechanistic distinction represents the structural basis for L858R’s unique vulnerability to dimerization interference. LP-300 is a disulfide-active small molecule whose metabolites, generated in the pericellular space, form covalent adducts with exposed cysteine residues on target proteins. The EGFR extracellular domain contains 50 cysteine residues forming 25 disulfide bonds — a structurally dense region that includes the dimerization arm through which EGFR receptors make receptor-to-receptor contact during the dimerization process. LP-300’s covalent activity at this extracellular interface provides a plausible mechanistic basis for disrupting dimerization itself, independent of the intracellular ATP-binding pocket where all currently approved EGFR inhibitors act.

These observations offer a coherent scientific hypothesis for the selectivity observed in the HARMONIC study: L858R tumors uniquely require dimerization for activation; LP-300’s covalent mechanism operates at the extracellular interface where that dimerization occurs; and the consequent attenuation of dimerization-driven signaling would be expected to selectively disadvantage L858R tumors in a manner that Exon 19 deletion tumors — which activate independently of dimerization — would not experience.

Lantern acknowledges this remains a mechanistic hypothesis requiring further experimental validation. The Company intends to incorporate mechanistic and advanced liquid biopsy studies within the amended HARMONIC protocol to further characterize this relationship as the trial advances.

Three Proposed Protocol Amendments

The following protocol amendments are being proposed to the FDA, each supported by clinical evidence and by the rapidly evolving treatment landscape for TKI-refractory NSCLC. Lantern is seeking FDA feedback and concurrence on these proposed amendments as part of the mid-May Type C meeting.

Focus Future Trial Enrollment to EGFR Exon 21 L858R Patients. Exploratory analysis from HARMONIC demonstrates that this mutation-defined subgroup derives a meaningfully greater and more consistent benefit from the LP-300 triplet regimen compared with other EGFR-mutant patients enrolled in the trial, including those with Exon 19 deletions. A multivariable Cox regression analysis confirms that L858R mutation status is an independent predictor of progression-free survival, even after adjusting for potential confounders. This supports a biomarker-driven enrollment strategy consistent with contemporary precision oncology trial design.
Convert to a Phase 2 Single-Arm Simon Two-Stage Study Design. The rapid global adoption of more recently approved combination regimens for TKI-refractory EGFR mutant NSCLC has made continued randomization to the control arm — carboplatin and pemetrexed alone — increasingly untenable both scientifically and operationally.
Increase LP-300 Treatment Cycles from 6 to 8. Exploratory data from HARMONIC indicate that L858R patients completing 6 cycles of LP-300 regimen demonstrated an mPFS of 8.9 months — higher than the overall L858R cohort median — with a comparable safety profile to those completing fewer cycles. This dose-duration relationship is consistent with LP-300’s kinase inhibitory mechanism of action. Historical safety data from prior LP-300 clinical trials also confirms that up to eight doses administered at the current dose level using the current dosing interval did not alter the established safety profile of the drug.
A Substantially Cleaner Tolerability Profile

LP-300 adds no new or clinically significant toxicity to the carboplatin and pemetrexed chemotherapy backbone. When the HARMONIC safety data to date is reviewed alongside published safety data from recently approved combination regimens in the TKI-refractory NSCLC setting, the contrast in treatment burden is clinically striking. The following comparison is based on available published data and reflects a review of LP-300’s safety profile versus a reference regimen from a larger randomized trial in a comparable, though not identical, patient population (Passaro et al., Annals of Oncology, 2024).

Lantern Pharma emphasizes that cross-trial safety comparisons should be interpreted with caution given potential differences in patient populations, study design, and data collection.

The select highlights in the table below summarize pertinent safety observations (>20%) regarding Treatment-Emergent Adverse Events (TEAE) that were determined to be Treatment Related Adverse Events (TRAE). A Treatment-Emergent Adverse Event in clinical trials is an unfavorable medical occurrence that starts or worsens in intensity or frequency after the first dose of study treatment.

Adverse Event Parameter

LP-300 + Carbo/Pem (N=31)

Reference Regimen* (N=130)

Treatment-Related SAE

1 (3%)

30 (23%)

Rash (TRAE)

2 (7%)

56 (43%)

Paronychia (TRAE)

0 (0%)

47 (36%)

*Reference regimen data: Passaro A, et al. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. 2024;35(1):77–90. Direct comparisons between trials should be made with caution given differences in patient populations, study design, and enrollment criteria.

For patients who have already navigated prior lines of therapy, treatment burden and quality of life are not secondary considerations. The ability to deliver comparable clinical activity with a substantially cleaner tolerability profile represents a meaningful point of differentiation in a therapeutic setting that has historically been associated with significant treatment-related morbidity.

Addressing a Large and Growing Unmet Need in EGFR-Mutant Lung Cancer

EGFR-mutant non-small cell lung cancer is one of the largest molecularly defined oncology markets globally, with approximately 350,000 new cases diagnosed annually worldwide. The EGFR Exon 21 L858R mutation — the subgroup demonstrating the most consistent observed benefit to date from LP-300 in HARMONIC — accounts for approximately 40% of all EGFR-mutant NSCLC cases, representing an estimated 90,000 to 100,000 patients per year.

The commercial significance of this population is growing. As osimertinib has become the established frontline standard of care globally, a substantial and increasing number of patients are completing first-line treatment and entering the post-TKI setting — the precise setting where HARMONIC data point to LP-300’s greatest potential clinical activity. The L858R subgroup carries a particularly poor prognosis following osimertinib failure, and existing approved options in this setting are associated with significant tolerability challenges that may limit real-world use and patient quality of life.

The market opportunity is further amplified by geography. The L858R mutation is disproportionately represented among never-smokers, who account for 35 to 40% of all NSCLC cases in Asia compared with approximately 15 to 17% in the United States and Europe. Lantern is evaluating patients across clinical sites in the United States, Japan, and Taiwan, and is exploring regional and global collaboration opportunities to maximize LP-300’s commercial potential across these geographies.

The treatment of never-smokers with NSCLC represents an estimated $4 billion or more in annual market opportunity. Lantern believes LP-300’s emerging profile — combining a consistent mutation-selective efficacy signal with a substantially differentiated tolerability profile — positions it as a potentially meaningful treatment option for a patient population with significant unmet need.

Biological Refinement: The Never-Smoker and L858R Intersection

HARMONIC was originally designed to address a critically underserved population: never-smokers with TKI-refractory NSCLC, for whom no therapy has been specifically approved. The EGFR L858R mutation is substantially enriched in never-smoker populations — particularly in Asian patient cohorts where never-smokers represent 35 to 40% of all NSCLC cases. The proposed enrollment further refines this mission; it resolves the never-smoker thesis molecularly into a more precise patient definition, concentrated on the subgroup where LP-300 appears most consistently active and beneficial.

Management Commentary

"The patients participating in HARMONIC are facing a serious illness with real courage, and often with few remaining options. Their willingness to take part in this research is what makes progress possible, and it is the reason we approach this work with both urgency and humility.

The emerging data in patients with the EGFR L858R mutation — an 8.3-month progression-free survival signal in a post-TKI setting, without additional toxicity burden — is an encouraging early finding. We understand that this is preliminary data in a small patient cohort, but the signal is consistent with the biology, and it warrants a focused, disciplined development path.

Our Type C meeting with the FDA is a collaborative step in that direction. We want their input, we respect their process, and our goal is straightforward — to determine whether LP-300 can make a meaningful difference for patients who are running out of options, and to get there as efficiently as we can."

— Panna Sharma, President and Chief Executive Officer, Lantern Pharma Inc.

Collaboration and Partnership Opportunities

Lantern Pharma is actively exploring collaboration and partnering opportunities — both globally and regionally — to maximize LP-300’s commercial potential across multiple geographies. The Company’s RADR AI platform, which integrates multi-omic biomarker data with clinical outcomes, has been instrumental in confirming and better understanding the L858R signal and continues to inform patient selection strategy and combination approaches for LP-300.

About LP-300 and the HARMONIC Trial

LP-300 is an investigational agent being evaluated in Lantern Pharma’s Phase 2 HARMONIC trial in combination with carboplatin and pemetrexed in patients with advanced NSCLC who have progressed following TKI therapy. The trial includes patients across clinical sites in the United States, Japan, and Taiwan. LP-300 has not received FDA marketing approval. All clinical data referenced in this press release are preliminary and have not been source verified in their entirety; Data Cutoff: April 13, 2026.

(Press release, Lantern Pharma, APR 20, 2026, View Source;With-No-Added-Toxicity/default.aspx [SID1234664557])

On April 20, 2026 Debiopharm (www.debiopharm.com), a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow’s standard of care to cure cancer and infectious diseases, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to the combination of its PKMYT1 inhibitor, lunresertib (Debio2513), and its WEE1 inhibitor, zedoresertib (Debio 0123).

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The designation is for the treatment of adult patients with CCNE1 amplified, or a deleterious mutation in either FBXW7 or PPP2R1A, platinum-resistant/refractory ovarian cancer.

The FDA’s Fast Track program is designed to facilitate the development and expedite the review of new drugs intended to treat serious conditions and fill an unmet medical need. Programs granted Fast Track designation benefit from more frequent communication with the FDA and, if relevant criteria are met, may be eligible for Priority Review and Accelerated Approval of a New Drug Application (NDA).

Momentum Following AACR (Free AACR Whitepaper) Oral Presentation

This regulatory milestone follows the first clinical data disclosure from the MYTHIC Study (NCT04855656), a Phase I trial evaluating the lunresertib and zedoresertib combination in patients with advanced solid tumors harboring these specific genomic alterations. The data were featured yesterday in an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting by Dr. Timothy A. Yap, Medical Oncologist and Physician-Scientist at The University of Texas MD Anderson Cancer Center, and Principal Investigator of the MYTHIC study.

"The FDA’s decision to grant Fast Track designation for this combination therapy validates our synthetic lethality approach to treating high-unmet-need cancers," said Esteban Rodrigo Imedio, Executive Medical Director, Oncology, Debiopharm. "Coming immediately after Dr. Yap’s presentation of the MYTHIC data at AACR (Free AACR Whitepaper), this designation highlights the potential of combining lunresertib and zedoresertib to provide a meaningful new clinical option for patients with biomarker-selected ovarian cancer who have exhausted platinum-based therapies."

Addressing Unmet Need in Ovarian Cancer

Platinum-resistant or refractory ovarian cancer remains one of the most challenging malignancies to treat, with limited effective options for patients whose tumors have developed resistance. By targeting the DNA Damage Response (DDR) pathway through the dual inhibition of PKMYT1 and WEE1, the lunresertib/zedoresertib combination aims to exploit specific genomic vulnerabilities (CCNE1, FBXW7, or PPP2R1A) to induce tumor cell death.

ABOUT DNA DAMAGE REPAIR (DDR)

When cells have damaged DNA, they must undergo a repair process known as DDR to survive. Cancer cells rely heavily on DDR as they divide and grow uncontrollably. Inhibition of DDR, particularly in combination with other anticancer agents, prevents cancer cells from repairing their DNA, ultimately activating a programmed cell death process. DDR inhibitors such as zedoresertib (Debio 0123), Debiopharm’s WEE1 inhibitor, are currently being investigated in clinical and preclinical studies.

ABOUT PKMYT1 INHIBITION

Lunresertib (Debio2513) is a first-in-class, oral PKMYT1 inhibitor designed to exploit specific genetic vulnerabilities in solid tumors, such as CCNE1 amplification. By targeting PKMYT1, the drug induces synthetic lethality, preventing cancer cells from repairing DNA damage and forcing them into programmed cell death. As the most advanced PKMYT1 inhibitor in clinical development, lunresertib has shown encouraging proof-of-concept results both as monotherapy and in combination therapies within the ongoing MYTHIC trial.

(Press release, Debiopharm, APR 20, 2026, View Source [SID1234664574])

On April 20, 2026 Immuneering Corporation (Nasdaq: IMRX), a late-stage clinical oncology company focused on keeping cancer patients alive and helping them thrive, reported the presentation of new genetic data at the 2026 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 17-22, 2026 in San Diego, CA.

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"Atebimetinib is designed to promote survival by three mechanisms: shrinking tumors durably, preserving body mass by counteracting muscle wasting, and maintaining performance status by maximizing tolerability," said Ben Zeskind, Ph.D., Chief Executive Officer of Immuneering. "We believe these characteristics have the potential to both yield the best survival in the first-line, and to give patients the best chance of reaching and benefitting from second-line treatment. Today’s data at AACR (Free AACR Whitepaper) add genetic rationale to support atebimetinib’s observed durable tumor shrinkage and its optimal use in the first-line setting by showing that the most common RAS-inhibitor resistance mechanisms are rarely seen in atebimetinib-treated patients."

Inhibitors of RAS, RAF, or MEK often provide only temporary benefit due to pervasive resistance, as tumors acquire new mutations or mechanisms of escape within the MAPK pathway. Atebimetinib, a novel Deep Cyclic Inhibitor of MEK, is engineered to mitigate the selective pressure that typically drives these resistance mechanisms, with the goal of more durable anti-tumor activity. Immuneering presented circulating tumor DNA (ctDNA) data from 123 patients treated with atebimetinib, showing that acquired MAPK pathway alterations are rarely seen. These findings suggest that Deep Cyclic Inhibitors have the potential to overcome the limitations of conventional MAPK inhibition and provide a more sustained clinical benefit for patients, while potentially preserving sensitivity to subsequent treatments.

Key Findings from the AACR (Free AACR Whitepaper) Presentation:

Rare MAPK pathway reactivation: Across 86 patients treated with atebimetinib monotherapy and 37 patients treated in combination with chemotherapy, emergent and acquired mutations rarely converged on the RAS/MAPK pathway, in contrast to what is commonly observed with chronic RAS-targeted therapies.
Diffuse, non-convergent resistance patterns: Emergent resistance following atebimetinib treatment utilized a variety of non-MAPK pathways, rather than converging on a single escape mechanism.
Limited early adaptive resistance: ctDNA analysis showed minimal early molecular evolution during treatment, indicating that atebimetinib is not driving adaptive resistance and may impose less selective pressure than continuous pathway inhibition.
Taken together, the data position atebimetinib as a differentiated MEK inhibitor with potential to drive deep and durable antitumor activity.
"Our AACR (Free AACR Whitepaper) data further validate the scientific foundation of our platform, demonstrating that Deep Cyclic Inhibition can fundamentally alter how tumors evolve under therapy, unlocking opportunities to improve treatment durability," said Brett Hall, Ph.D., Chief Scientific Officer of Immuneering. "Deep Cyclic Inhibition of MEK avoids the continuous selective pressure that typically drives tumors to become resistant to treatment via reactivation of the MAPK pathway. This, combined with atebimetinib’s tolerability profile, has the potential to improve depth and durability of response in a broad range of cancers, starting with first-line pancreatic cancer."

Poster Presentation Details:
Title: Atebimetinib’s Deep Cyclic Inhibition of MEK Constrains MAPK-Axis Adaptive and Acquired Alterations in Patients with RAS-Mutant Tumors
Session Category: Experimental and Molecular Therapeutics
Session Title: Targeting Drug Resistance 2: RAS Signaling
Poster Number: 1873
Poster Board Number: 6
Session Date: April 20, 2026
Session Time: 9:00 AM – 12:00 PM ET
Location: Poster Section 19

The poster is available on the publications section of Immuneering’s website at View Source

Immuneering has guided to dosing the first patient in its pivotal Phase 3 MAPKeeper 301 trial of atebimetinib plus modified gemcitabine/nab-paclitaxel (mGnP) in patients with first-line metastatic pancreatic cancer in mid-2026. In the second half of the year, the company expects to dose the first patient in a Phase 2 trial of atebimetinib plus Libtayo in patients with first-line RAS-mutant non-small cell lung cancer.

(Press release, Immuneering, APR 20, 2026, View Source [SID1234664541])