Lantern Pharma Receives Successful Response To Its Recent FDA Type C Meeting Request Focused On The Ongoing Phase 2 HARMONIC Trial Of LP-300 In Never-Smokers With Advanced Non-Small Cell Lung Cancer Adenocarcinoma

In its written responses to Lantern's Type C meeting request, the FDA raised no objections to key proposed protocol amendments, providing a more focused, clearer regulatory path forward for the HARMONIC™ trial and for the future development of LP-300 in this distinct, high-need patient population.

The HARMONIC™ trial is designed to evaluate LP-300, a small molecule given in combination with carboplatin and pemetrexed, in never-smokers with advanced NSCLC adenocarcinoma who have experienced disease progression following treatment with kinase inhibitors. Never-smoker NSCLC is increasingly recognized as a distinct disease entity with unique clinical and genomic features. Globally, approximately 400,000 to 500,000 patients are diagnosed with never-smoker NSCLC each year — a patient population that, if classified separately, would rank among the most common cancers worldwide. Despite this scale, no therapies have been specifically developed or labeled for the never-smoker NSCLC patient population, and the EGFR exon 21 L858R subset in particular continues to experience inferior outcomes when treated with currently available standards of care.

"In our view, this successful Type C interaction with the FDA is a meaningful de-risking milestone for the LP-300 program and for the HARMONIC™ trial. The FDA's response to our proposed amendments supports our strategy to focus HARMONIC™ on the EGFR exon 21 L858R-mutant never-smoker population, where emerging data suggest LP-300 may offer meaningful differentiated benefit when added to standard chemotherapy following TKI failure."

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

Focused Enrollment in EGFR Exon 21 L858R Never-Smokers

Under the amended protocol supported by the FDA's Type C responses, Lantern plans to focus all future HARMONIC™ enrollment on patients harboring the EGFR exon 21 L858R mutation, a subtype of EGFR kinase domain mutations associated with lower TKI binding affinity and inferior outcomes on osimertinib-based therapy relative to patients with exon 19 deletions. Preliminary analyses from the ongoing HARMONIC™ trial suggest that patients with EGFR exon 21 L858R-mutant disease may derive greater clinical benefit from the LP-300 triplet regimen than other EGFR-mutant subgroups, providing a biologically and clinically compelling rationale to enrich the study for this population. Based on currently available data, preliminary multivariable Cox regression analyses incorporating race, gender, and TP53 mutation status have confirmed L858R as an independent predictor of progression-free survival benefit in the trial, suggesting the signal is not driven by demographic confounders.

"The preliminary signal in the EGFR exon 21 L858R cohort — including a median progression-free survival of 8.3 months and durable responses extending beyond two years in select patients — gives us confidence that an enriched, single-arm design is the right next step. Aligning the trial with that signal, and receiving no objection from the FDA to key aspects of our approach via a successful Type C interaction, positions us to generate a more focused, decision-enabling data-set for patients, regulators, and potential partners."

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

Extended LP-300 Dosing Based on Safety and Emerging Outcomes

In addition to refining the molecularly defined patient population, the Type C feedback supports Lantern's proposal to increase the maximum number of LP-300 treatment cycles in HARMONIC™ from six to eight. This change is supported by historical safety data from prior clinical experience with LP-300 indicating that up to eight cycles at the current dose level did not alter the established safety profile of the drug, as well as by emerging HARMONIC™ data suggesting improved outcomes with longer LP-300 treatment duration.

By extending LP-300 dosing, Lantern aims to maximize the depth and durability of response without adding clinically meaningful toxicity beyond that expected with carboplatin and pemetrexed alone. In earlier studies, LP-300 has been administered in multiple clinical trials to more than 1,000 individuals and has generally been well tolerated, providing a substantial safety foundation for this dosing adjustment.

Transition to a Single-Arm, Enriched Study Design

As part of the protocol amendments proposed in the Type C meeting interaction, Lantern will discontinue enrollment into the control arm of the HARMONIC™ trial and migrate the study into a single-arm design that only enrolls additional patients with the EGFR exon 21 L858R mutation. This evolution reflects the rapidly changing treatment landscape in TKI-refractory NSCLC, where increasing availability of subsequent-line therapies and patient preferences have made continued randomization to a traditional chemo-doublet control arm operationally challenging in never-smokers.

The enriched, single-arm design is intended to accelerate enrollment, sharpen the clinical signal within a genomically defined subgroup, and enable more efficient comparisons to historical and real-world benchmarks in EGFR exon 21 L858R-mutant never-smoker NSCLC. Lantern anticipates that the amended design, coupled with continued integration of AI-driven insights from its RADR® platform, will support more informed discussions with regulators and prospective collaborators regarding potential registration-oriented strategies for LP-300.

Differentiated Safety Profile vs. Currently Approved Post-TKI Combinations

A central commercial rationale for the focused HARMONIC™ design is the differentiated safety profile of LP-300 plus chemotherapy relative to currently approved post-TKI regimens. In the recently published Phase 3 MARIPOSA-2 trial, amivantamab plus chemotherapy — now FDA-approved for EGFR-mutant NSCLC following progression on osimertinib — was associated with substantial rates of treatment-related serious adverse events, infusion reactions, and dermatologic toxicities that complicate real-world administration. Preliminary HARMONIC™ data (Data Cutoff: April 13, 2026; n=31 receiving LP-300 + chemotherapy) suggest a materially more manageable safety profile when LP-300 is added to a carboplatin/pemetrexed backbone:

The table below summarizes observations regarding Treatment-Related Adverse Events (TRAE) and Treatment-Emergent Adverse Events (TEAE). 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.