Category: 8. Health

Specialty

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This study provides an up-to-date evaluation on the global, regional, and national burden of early-onset CVD attributable to PM_2.5 from 1990 to 2021. Males, individuals living in regions with lower SDI, and those with IHD experience a higher burden. Over the past three decades, there was a substantial decrease in early-onset CVD burden attributable to total and household PM_2.5, especially in regions with higher SDI. However, the corresponding burden from ambient PM_2.5 continued to rise and only began to decline since the last decade. In addition, the reduction in early-onset CVD burden was less prominent than that of late-onset CVD. Such findings underscore that even in the context of global population aging, the PM_2.5-related early-onset CVD burden remains a critical concern.

Most previous studies focused on the overall CVD burden attributable to PM_2.5, with few age-specific analyses and insufficient attention to younger populations [13, 15, 21]. Besides, there has been a decreasing trend in the all-age CVD death and DALY rates attributable to both ambient and household PM_2.5 exposure over the past three decades [9]. However, how the early-onset CVD burden varied across different regions and time periods remains unclear. Our study is the first to fill this gap by conducting a comprehensive analysis of early-onset CVD burden attributable to PM_2.5 from 1990 to 2021 at the global level. We also present the late-onset CVD burden and age-specific burden by 5-year intervals. The results show that the attributable burden was consistently higher in older age groups, suggesting their greater susceptibility. Interestingly, while the burden of both early- and late-onset CVD from total and household PM_2.5 has declined, the reduction in the early-onset burden is smaller compared to the late-onset burden. Additionally, in contrast to the decline in late-onset CVD burden, the early-onset CVD burden due to ambient PM_2.5 even increased slightly. This suggests a need for sustained attention to younger populations who may experience slower improvements despite lower absolute burden.

Our study reveals obvious sexual differences in the burden of early-onset CVD attributable to PM_2.5 pollution. In general, males experience a higher burden compared to females, which is consistent with higher PM_2.5-related CVD risk among males reported in previous researches [22,23,24]. This between-sex difference is more pronounced for ambient PM_2.5 pollution and less prominent for household PM_2.5. Several factors might contribute to this heterogeneity. First, there is generally a higher prevalence of traditional cardiovascular risk factors among males, such as hypertension, alcohol consumption, and smoking, which contributed to a higher overall CVD burden [9, 25, 26]. Second, social and occupational factors might also play an important role. Men are more likely to engage in outdoor labor-intensive work, leading to greater exposure to ambient air pollution. Conversely, women are more often exposed to indoor air pollution due to their involvement in household tasks such as cooking [27, 28]. These results underscore the importance of accounting for sex-specific exposure patterns when designing public health policies aimed at reducing PM_2.5-related disease burdens. Reducing ambient PM_2.5 exposure is particularly important for mitigating CVD burden among men, while minimizing both ambient and indoor exposure would be equally crucial for women.

Substantial variations by SDI were illustrated in the burden of early-onset CVD attributable to PM_2.5 pollution. Similar to patterns observed in studies on other non-communicable diseases [29], a reversed U-shaped association was found between SDI and the early-onset CVD burden attributable to ambient PM_2.5. In contrast, the corresponding burden due to household PM_2.5 showed a generally decreasing trend as SDI increased. Low-SDI regions in Sub-Saharan Africa and South Asia faced the highest burden from household PM_2.5, while middle-SDI regions in North Africa, the Middle East, South Asia, and East Asia experienced the greatest burden from ambient PM_2.5. This pattern could be explained by the regional economic and environmental differences. Specifically, low-SDI countries, largely dependent on solid fuels, have higher household PM_2.5 exposure, whereas middle-SDI countries face increased ambient pollution due to rapid urbanization and industrialization [30, 31]. High-SDI regions had the lowest burden from both ambient and household PM_2.5, which might be largely due to the use of cleaner energy, stricter environmental regulations, more resources of individual protective measures, and improved public health and clinical systems. These regional differences underscore the critical influence of socioeconomic development on the early-onset CVD burden attributable to PM_2.5 pollution.

To effectively mitigate the early-onset CVD burden due to PM_2.5 pollution, tailored air quality policies and interventions based on regional economic and environmental contexts are warranted. In low-SDI countries, international cooperation is essential, including technology transfer to promote clean cooking stoves, clean energy use, and improved household ventilation. Global financial support is also needed to subsidize infrastructure upgrades and clean energy transitions. For middle-SDI countries undergoing rapid industrialization and urbanization, stringent air quality management plans including tightening industrial emission standards, expanding public transportation systems, and promoting clean energy transitions are needed. High-SDI countries, while facing relatively lower PM_2.5 burdens, should continue strengthening environmental regulations, advancing control technologies, and investing in long-term pollutant management. They can also play a leading role in supporting global air pollution control efforts through research collaboration, funding, and cross-border policy communication.

The health effects and corresponding disease burden attributable to PM_2.5 may also vary depending on its chemical composition and sources, which differ substantially across regions [32]. Previous studies reported that carbonaceous components and PM_2.5 from fossil fuel combustion might pose higher cardiovascular risks [33,34,35,36], which could theoretically contribute to a higher disease burden. However, due to data limitations, our analysis focused on total PM_2.5 mass and did not account for the heterogeneity in chemical constituents and sources. This limitation may also contribute to uncertainties in regional burden estimates. Future studies integrating data on PM_2.5 chemical composition and source-specific toxicity are warranted to improve the precision of disease burden estimates and guide more targeted interventions.

Over the past three decades, there has been a significant decrease in the early-onset CVD burden attributable to total and household PM_2.5 pollution, especially in regions with higher SDI levels. In contrast, the burden from ambient PM_2.5 slightly increased at the global level, which was mainly driven by increasing burden in less-developed regions [31]. Since the year 2012, early-onset CVD burden from ambient PM_2.5 has exceeded that from household PM_2.5, and became the primary contributor to PM_2.5-related burden. This shift illustrates the effectiveness of the global efforts in promoting cleaner energy sources including natural gas and electricity for household use, and emphasizes that stricter actions especially on ambient PM_2.5 pollution are needed to reduce CVD burden in the future.

This study provides a comprehensive and up-to-date evaluation on the global, regional, and national distributions and temporal trends of early-onset CVD burden from PM_2.5 exposure. Our findings offer scientific guidance for multiple fields, including public health, clinical practice, and environmental health policy, in developing targeted interventions and management strategies to promote global cardiovascular health.

There are several limitations that should be acknowledged. First, PM_2.5 is a complex mixture comprising multiple constituents, each with distinct physicochemical properties [37]. The composition of PM_2.5 can vary significantly by source, season, and region [38, 39]. However, the GBD 2021 study assumes spatial homogeneity in PM_2.5 composition, potentially leading to inaccurate estimations in specific locations [29]. Future studies should take the heterogeneity of PM_2.5 composition and source into consideration when evaluating the disease burden attributable to PM_2.5. Second, our assessment of household PM_2.5 pollution did not account for solid fuel use for heating, which is also an important contributor to indoor air pollution and a known risk factor for CVD [9, 40]. Thus, future studies should explore the contribution of solid fuel use for heating to the disease burden attributable to household PM_2.5 pollution. Third, the effect estimates in this study rely on available epidemiological datasets, which might be limited in many low- and middle-income regions. Issues such as underdiagnosis and inadequate health care access could lead to biases in the estimation. Fourth, the current GBD 2021 dataset only evaluates burden of IHD as an aggregated category. Therefore, we were unable to estimate the disease burden by finer subtypes of IHD such as acute myocardial infarction, angina, or chronic IHD separately. In addition, most existing cohort studies on air pollution have focused on overall IHD rather than its specific subtypes, leading to insufficient evidence supporting more detailed burden estimation. Therefore, future studies with finer disease categories are warranted and would be valuable to inform targeted interventions. Last, while the relative risk estimates used in GBD 2021 were derived from epidemiological studies that adjusted for major confounders, residual confounding from unmeasured factors may still exist. In addition, potential interactions and mediation among different risk factors are not fully captured in these models. Future studies incorporating more detailed covariate data and advanced analytical methods are needed to better account for residual confounding and to explore these complex relationships.

Introduction

Metal allergies can cause inflammatory conditions affecting the skin and mucous membranes, often complicating diagnoses when associated with dental prostheses. Differentiating between allergic reactions to dental metals and other inflammatory lesions, such as oral lichen planus, can be difficult in the oral cavity. Oral lichen planus is a chronic inflammatory condition with multiple possible etiologies, including autoimmune responses, infections, medications, and, in some cases, metal allergies.

Previous studies have reported an association between dental metal restorations and oral lichen planus, leading to the recommendation of metal removal as a treatment option.¹ However, the persistence of symptoms following metal removal suggests that other pathologies, such as oral lichen planus, may play a more significant role.² This case report presents a patient with persistent oral lesions initially attributed to metal allergies, where treatment targeting the suspected allergy was unsuccessful, ultimately revealing oral lichen planus as the primary diagnosis.

Patients and Methods

Patient Information

A 55-year-old female patient presented with redness and pain in the buccal gingiva near the right mandibular first molar (#46). Her medical history included atrophic gastritis, and she had a known metal allergy. The patient had no previous history of oral lichen planus. The patient’s family history was unremarkable.

Present Illness

The patient was referred to our department from a dermatology clinic specializing in allergies and presented with symptoms suggestive of a metal allergy, including redness and lace-like white patches on the buccal gingiva adjacent to tooth #46. Redness and lace-like white patches were observed on the buccal gingiva near tooth #46, accompanied by pain and inflammation (Figure 1).

Figure 1 Redness and lace-like white patches on the buccal gingiva near tooth #46, with associated pain and inflammation.

Clinical Findings

Upon intraoral examination, full-cast crowns were identified on teeth #16, #17, #26, #27, #36, #37, #46, and #47, whereas partial-cast crowns were found on teeth #24, #25, #34, and #35 using the FDI two-digit tooth numbering system.³ Tooth #45 was restored with a composite resin, and the remaining teeth were natural (Figure 2). No extra-oral abnormalities were observed.

Figure 2 Full cast crowns on teeth #16, #17, #26, #27, #36, #37, #46, and #47, and partial cast crowns on teeth #24, #25, #34, and #35. Composite resin restoration on tooth #45.

Intraoral Metal Element Analysis

Samples were collected from all intraoral restorations using a silicone point (M3-28, Shofu, Kyoto) and analyzed using an X-ray fluorescence spectrometer (MESA-500W, HORIBA, Kyoto). The analysis detected the presence of Zn and Co in full-cast crowns on teeth #16, #17, #26, #27, #36, #37, #46, and #47, as well as in partially-cast crowns on teeth #24, #25, and #34 (Table 1).

Table 1 Intraoral Metal Element Analysis of Dental Crowns

Diagnosis and Treatment

Based on the intraoral metal element analysis, a diagnosis of metal allergy was confirmed.⁴ In September 2021, the metal crowns were removed and replaced with provisional restorations made of autopolymerizing resin. During the crown removal, suction, gauze, and an extraoral vacuum were employed to prevent exposure to metal fragments. No acute symptoms were observed postoperatively. Full-zirconia ceramic crowns were placed in December 2021. However, redness and pain persisted even eight months after crown placement (Figure 3).

Figure 3 Persistent redness and pain in the buccal mucosa eight months after zirconia crowns were placed on teeth #46.

Subsequently, in August 2022, the metal crown of the right mandibular second molar (#47) was removed and replaced with a full zirconia ceramic crown, similar to the approach used for tooth #46 (Figure 4). Despite these interventions, the symptoms did not subside, prompting reconsideration of the initial diagnosis. The patient was referred to the Department of Oral and Maxillofacial Surgery.

Figure 4 White patches remained on the oral mucosa after the healing of oral lichen planus.

Further Diagnostic Evaluation and Outcome

In November 2022, a punch biopsy was performed, which confirmed a diagnosis of oral lichen planus through histopathological analysis. Subsequently, the oral surgeon initiated steroid therapy, including dexamethasone 0.1% oral ointment and azunol 4% mouthwash. Regular follow-up (monthly) showed gradual resolution of the mucosal inflammation, and by March 2023, the oral lichen planus had fully healed (Figure 5). The patient was continuously monitored for recurrence.

Figure 5 Oral cavity overview after the healing of oral lichen planus.

Results

This case represents an unusual presentation of oral lichen planus that was initially diagnosed as a metal allergy-induced lesion. The removal of dental metals and their replacement with zirconia crowns did not lead to symptom improvement, suggesting that metal allergy was not the sole cause of the patient’s symptoms. Successful resolution following steroid therapy supports the hypothesis that oral lichen planus rather than metal allergy is the primary pathology.

Discussion

Dental metal allergies can manifest in various ways, and management approaches should take into account factors such as mucocutaneous symptoms, the involvement of allergy-positive metals, and individual patient response to the removal of dental metals.⁵ In this case, despite the detection of allergy-positive metals (Zn and Co), mucosal inflammation persisted following metal removal. This finding underscores the need for a comprehensive approach to diagnosing oral lesions, particularly in patients with complex presentations.⁶ Differential diagnoses considered included lichenoid contact reaction, systemic lupus erythematosus, and mucous membrane pemphigoid. These were ruled out based on clinical presentation and histopathological features. Oral lichen planus has been linked to various etiologies beyond metal allergies, including bacterial and viral infections, medications, stress, and autoimmune diseases.⁷ In cases where metal allergy is suspected, but symptoms persist despite the allergen removal, other potential causes, such as oral lichen planus, must be carefully evaluated. In this case, the efficacy of steroid therapy highlights the importance of considering alternative treatments, including immunosuppressants, antiviral medications, and biologics, especially in patients who do not respond to conventional therapies.⁸

Chronic oral lichen planus can severely impact a patient’s quality of life due to persistent pain and discomfort.⁹ Therefore, treatment goals should not only focus on symptom relief and recurrence prevention but also on improving the patient’s overall quality of life. Patient education and regular follow-ups are essential components of long-term management.¹⁰

Conclusion

This case highlights the need for a multidisciplinary approach to manage oral inflammatory conditions. Prosthodontists and dental practitioners should consider various perspectives and collaborate with other departments when facing persistent oral lesions, particularly when treatments targeting suspected metal allergies fail to yield positive results and desired outcomes. Alternative diagnoses, such as oral lichen planus, should be considered, and appropriate interventions should be implemented to achieve optimal patient care.

Acknowledgments

We would like to express our gratitude to Dr. Kitagawa from the Center of Oral Clinical Examination and Dr. Taguchi from the Department of Oral and Maxillofacial Surgery for their dedicated efforts in managing this condition.

Additionally, the patient provided written informed consent for the publication of this case report, including the use of clinical images. Ethical approval was not required for this case report, as no identifiable personal information is disclosed, and institutional guidelines at Hiroshima University Hospital do not require IRB review for single case reports.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

References

1. Sugiyama M, Kawashima A, Ishida K, et al. Clinical features of oral lichen planus related to dental metal restorations. Oral Sci Int. 2012;9(2):81–85.

2. Kato T, Matsuda S, Ishikawa J, et al. Refractory oral lichen planus after dental metal replacement: a retrospective study. J Dermatol. 2020;47(5):506–512.

3. FDI World Dental Federation. FDI two-digit tooth numbering system. Int Dent J. 1971;21(1):104–106.

4. Sakanashi EN, Kikuchi K, Matsumura M, et al. Chapter 7-Allergic contact dermatitis to dental alloys: evaluation, diagnosis and treatment in Japan — reflectance confocal laser microscopy, an emerging method to evaluate allergic contact dermatitis. In: Confocal Laser Microscopy – Principles and Applications in Medicine, Biology, and the Food Sciences. 2013.

5. Akiba Y, Watanabe M, Mine A, et al. With the aim of treatment guideline development for dental metal allergy and related diseases. Ann Jpn Prosthodont Soc. 2016;8(4):327–339. doi:10.2186/ajps.8.327

6. Stone SJ, McCracken GI, Heasman PA, et al. Cost-effectiveness of personalized plaque control for managing the gingival manifestations of oral lichen planus: a randomized controlled study. J Clin Periodontol. 2013;40:859–867. doi:10.1111/jcpe.12126

7. Louisy A, Humbert E, Samimi M. Oral lichen planus: an update on diagnosis and management. Am J Clin Dermatol. 2024;25:35–53. doi:10.1007/s40257-023-00814-3

8. Rotaru D, Chisnoiu R, Picos AM, et al. Treatment trends in oral lichen planus and oral lichenoid lesions (Review). Exp Ther Med. 2020;20:198. doi:10.3892/etm.2020.9328

9. Salgado DS, Jeremias F, Capela MV, et al. Plaque control improves the painful symptoms of oral lichen planus gingival lesions. A short-term study. J Oral Pathol Med. 2013;42:728–732. doi:10.1111/jop.12093

10. Hashemipour MA, Sheikhhoseini S, Afshari Z, et al. The relationship between clinical symptoms of oral lichen planus and quality of life related to oral health. BMC Oral Health. 2024;24:556. doi:10.1186/s12903-024-04326-2

Specialty

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• At extended median follow-up of 19.7 months, median overall survival (“OS”) increased from 16.33 to 28.94 months
• Clinical efficacy correlated with the magnitude of T cell responses specific to mutant-KRAS (“mKRAS”) induced by ELI-002
• 77% reduction in the risk of death and 88% reduction in the risk of relapse, associated with T cell responses above the threshold for anti-tumor efficacy
• ELI-002 induced both CD4+ and CD8+ mKRAS-specific T cell responses in most patients, and evidence of antigen-spreading to patient-specific neoantigens not included in ELI-002 was observed
• Final event-driven disease-free survival (“DFS”) analysis for the randomized Phase 2 AMPLIFY-7P study evaluating ELI-002 7P monotherapy in pancreatic ductal adenocarcinoma (“PDAC”) is anticipated in Q4 2025

BOSTON, Aug. 12, 2025 (GLOBE NEWSWIRE) — Elicio Therapeutics, Inc. (Nasdaq: ELTX, “Elicio” or the “Company”), a clinical-stage biotechnology company developing a pipeline of novel immunotherapies for the treatment of cancer, today announced the publication of follow-up data from the Phase 1 AMPLIFY-201 study evaluating ELI-002 in the peer-reviewed scientific journal, Nature Medicine. The article, entitled, “Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: Phase 1 AMPLIFY-201 trial final results,” highlights that with extended follow-up, more than two-thirds of participants (17 of 25) whose T cell responses exceeded the antitumor efficacy threshold experienced a significantly reduced risk for relapse or death.

“This publication, combined with the early promising clinical data we’ve generated to date, further strengthens our belief that our Amphiphile (“AMP”) platform represents a potentially transformative approach in the treatment of mKRAS-driven tumors,” commented Robert Connelly, Chief Executive Officer of Elicio.

Chris Haqq, MD, Ph.D., Chief Medical Officer of Elicio, added, “The updated Phase 1 AMPLIFY-201 data further demonstrate that the AMP platform has the potential to provide durable benefit to PDAC patients in the adjuvant setting. These promising results together with the recent positive recommendation from the Independent Data Monitoring Committee that the randomized ongoing Phase 2 AMPLIFY-7P study should continue without modification to final DFS analysis, represent critical advancements for our promising lead program.”

Key Findings:

• 25 adjuvant-stage patients with solid tumors (20 PDAC, 5 colorectal) were enrolled for treatment based on positive for minimal residual mKRAS disease after locoregional treatment, with data reported through September 24, 2024.
• Direct ex vivo mKRAS-specific T cell responses were observed in 21/25 patients (84%), including both CD4+ and CD8+ T cell responses in 71% of patients, and 6/6 patients (100%) treated at the recommended Phase 2 dose (“RPD2”); the induction of both CD4+ and CD8+ T cells correlated with overall tumor biomarker response (p<0.0035).
• Tumor biomarker responses were observed in 21/25 patients (84%), with complete biomarker clearance observed in 6/25 patients, as determined by tumor-informed circulating tumor DNA analysis (24%; 3 PDAC, 3 colorectal).
• At 19.7 months median follow-up (compared to 8.5 months previously), the median relapse-free survival (“RFS”) was 16.33 months, and the median OS was 28.94 months for the 25-patient cohort.
• Efficacy correlated with ELI-002-induced mKRAS-specific T cell response (≥ versus < threshold: 9.17-fold over baseline; threshold defined through receiver-operating curve analysis):
  • Median tumor biomarker reduction was 55.2% compared to 36.7% in above versus below threshold T cell responders, respectively (p<0.0024).
  • 11/17 patients with T cell response above threshold remained free from radiographic progression while 8/8 patients with below threshold T cell responses had confirm radiographic progression (7/8 had died); Relative Risk of Progression or Death in below threshold T cell responders was 2.96.
  • Median RFS was not reached compared to 3.02 months in above versus below threshold T cell responders, respectively (HR 0.12, 95% CI 0.02 to 0.62, p=0.0002); patients with greater than threshold T cell response had an 88% reduction in the risk of progression or death.
  • Median OS was not reached compared to 15.98 months in above versus below threshold T cell responders, respectively (HR 0.23, 95% CI 0.06 to 0.85, p=0.0099); patients with greater than threshold T cell response had an 77% reduction in the risk of death.
• Antigen-spreading, a process where the immune system, initially targeting the mKRAS antigens in ELI-002, expands its response to recognize additional antigens in the patient’s tumor leading to a broader and more effective anti-tumor response, was observed in 67% of patients, with increased T cells reactive to personalized, tumor neoantigens absent from ELI-002; overall, increased T cell responses were observed in 13/52 (25%) of evaluated tumor neoantigens.
• ELI-002 was well tolerated, with no safety concerns identified, and no dose-limiting toxicities or ≥ Grade 3 treatment-related adverse events were observed.

	Pant, et al. Nature Medicine. 2024	Wainberg, et al. Nature Medicine. 2025
DCO	6 Sept 2023	24 Sept 2024
Median Follow-up	8.5 months	19.7 months
Median RFS (n=25)	16.33 months	16.33 months
Median OS (n=25)	16.33 months	28.94 months
mKRAS T Cell Response Threshold	12.75x (median)	9.17x (ROC-defined)
Patients ≥ mKRAS T Cell Response Threshold	13/25	17/25
mKRAS T Cell Response Correlation to:
Tumor Biomarker Response	P=0.0014	P=0.0024
RFS	HR 0.14, P=0.0167	HR 0.12, P=0.0002
OS	NR	HR 0.23, P=0.0099

DCO: Data cut-off; RFS: Relapse-free survival; OS: Overall survival; ROC: Receiver-operating curve; NR: Not reported

Elicio Therapeutics, Inc. (Nasdaq: ELTX) is a clinical-stage biotechnology company advancing novel immunotherapies for the treatment of high-prevalence cancers, including mKRAS-positive pancreatic and colorectal cancers. Elicio intends to build on recent clinical successes in the personalized cancer vaccine space to develop effective, off-the-shelf vaccines. Elicio’s Amphiphile (“AMP”) technology aims to enhance the education, activation and amplification of cancer-specific T cells relative to conventional vaccination strategies, with the goal of promoting durable cancer immunosurveillance in patients. Elicio’s ELI-002 lead program is an off-the-shelf vaccine candidate targeting the most common KRAS mutations, which drive approximately 25% of all solid tumors. Off-the-shelf vaccine approaches have the potential benefits of low cost, rapid commercial scale manufacturing, and rapid availability of drug to patients especially in neo-adjuvant settings and for prophylaxis in high-risk patients, contrary to personalized vaccines approaches. ELI-002 is being studied in an ongoing, randomized clinical trial in patients with mKRAS-positive pancreatic cancer who completed standard therapy but remain at high risk of relapse. ELI-002 also has been studied in patients with mKRAS-positive colorectal cancer (“CRC”) in Phase 1 studies. The updated AMPLIFY-201 Phase 1 data for PDAC and CRC was presented at the ESMO Immuno-Oncology Congress 2024 and included a 16.3-month median recurrence-free survival and 28.9-month median overall survival for the full study population. In the future, Elicio plans to expand ELI-002 to other indications including mKRAS positive lung cancer and other mKRAS positive cancers. Elicio’s pipeline includes additional off-the-shelf therapeutic cancer vaccines candidates, including ELI-007 and ELI-008, that target BRAF-driven cancers and p53 hotspot mutations, respectively. For more information, please visit www.elicio.com.

About ELI-002

Elicio’s lead product candidate, ELI-002, is a structurally novel investigational AMP cancer vaccine that targets cancers that are driven by mutations in the KRAS-gene—a prevalent driver of many human cancers. ELI-002 is comprised of two powerful components that are built with Elicio’s AMP technology consisting of AMP-modified mutant KRAS peptide antigens and ELI-004, an AMP-modified CpG oligodeoxynucleotide adjuvant that is available as an off-the-shelf subcutaneous administration.

ELI-002 2P (2-peptide formulation) has been studied in the Phase 1 (AMPLIFY-201) trial in patients with high relapse risk mKRAS-driven solid tumors, following surgery and chemotherapy (NCT04853017). ELI-002 7P (7-peptide formulation) is currently being studied in a Phase 1/2 (AMPLIFY-7P) trial in patients with mKRAS-driven pancreatic cancer (NCT05726864). The ELI-002 7P formulation is designed to provide immune response coverage against seven of the most common KRAS mutations present in 25% of all solid tumors, thereby increasing the potential patient population for ELI-002.

About the Amphiphile Platform

Elicio’s proprietary AMP platform delivers investigational immunotherapeutics directly to the “brain center” of the immune system – the lymph nodes. Elicio believes this site-specific delivery of disease-specific antigens, adjuvants and other immunomodulators may efficiently educate, activate and amplify critical immune cells, potentially resulting in induction and persistence of potent adaptive immunity required to treat many diseases. In preclinical models, Elicio observed lymph node-specific engagement driving therapeutic immune responses of increased magnitude, function and durability. Elicio believes its AMP lymph node-targeted approach will produce superior clinical benefits compared to immunotherapies that do not engage the lymph nodes based on preclinical studies.

Elicio’s AMP platform, originally developed at the Massachusetts Institute of Technology, has broad potential in the cancer space to advance a number of development initiatives through internal activities, in-licensing arrangements or development collaborations and partnerships.

The AMP platform has been shown to deliver immunotherapeutics directly to the lymph nodes by latching on to the protein albumin, found in the local injection site, as it travels to lymphatic tissue.

Cautionary Note on Forward-Looking Statements

Certain statements contained in this communication regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995, known as the PSLRA. These include statements regarding Elicio’s planned clinical programs, including the timing and outcome of planned clinical trials; the timing of the expected event-driven final DFS analysis of the Phase 2 AMPLIFY-7P clinical trial; the potential of Elicio’s product candidates and platform, including the potential transformational approach Elicio’s AMP platform could represent in the treatment of mKRAS-driven tumors; the potential impact of the AMP Platform and ELI-002 in PDAC, including the potential for Elicio’s AMP platform to provide durable benefit for PDAC patients in the adjuvant setting; the potential for future expansion of ELI-002 to other indications, including mKRAS positive lung cancer and other mKRAS positive cancers; the potential benefits and effectiveness of off-the-shelf vaccine approaches; and other statements regarding management’s intentions, plans, beliefs, expectations or forecasts for the future and, therefore, you are cautioned not to place undue reliance on them. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Elicio undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise, except to the extent required by law. We use words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “continue,” “guidance,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions of the PSLRA. Such forward-looking statements are based on our expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including, but not limited to, Elicio’s plans to develop and commercialize its product candidates, including ELI-002; the timing of initiation of Elicio’s planned clinical trials; the timing of the availability of data from Elicio’s clinical trials, including the event-driven final DFS analysis from the Phase 2 AMPLIFY-7P trial anticipated in the fourth quarter of 2025; the timing of any planned investigational new drug application or new drug application; Elicio’s plans to research, develop and commercialize its current and future product candidates; and Elicio’s estimates regarding future revenue, expenses, capital requirements and need for additional financing.

New factors emerge from time to time, and it is not possible for us to predict all such factors, nor can we assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. These risks are more fully discussed under the heading “Risk Factors” in Elicio’s Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on March 31, 2025, our Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, filed with the SEC on May 13, 2025, and our Quarterly Report on Form 10-Q for the quarter ended June 30, 2025, filed with the SEC on August 7, 2025, as updated by subsequent reports and other documents filed from time to time with the SEC. Forward-looking statements included in this release are based on information available to Elicio as of the date of this release. Elicio does not undertake any obligation to update such forward-looking statements to reflect events or circumstances after the date of this release, except to the extent required by law.

Investor Relations Contact
Brian Ritchie
LifeSci Advisors
(212) 915-2578
britchie@lifesciadvisors.com 

New data from the CDC suggests a grim back-to-school tradition emerging: in 2024, kindergarten vaccination rates declined for the fifth consecutive year. Meanwhile, vaccine exemptions reached a record high.

These statistics became all the more disturbing last fall when, shortly after 286,000 children began their educations without proof of full immunity against measles, a man who has bragged about never getting a flu shot was re-elected to the presidency. Since then, the US has contended with its largest measles outbreak in three decades, while the leaders who should be stamping out this crisis are instead fanning the flames.

In just eight months, Trump and Robert F Kennedy Jr, secretary of the Department of Health and Human Services, have made every effort to undermine one of the major civilizing advances of the 20th century – our public health infrastructure. In doing so, they risk endangering millions of people and kickstarting a doom loop of mistrust from which it could take decades to recover.

As usual, the Trump administration’s stance on vaccines is motivated less by sincere populism and more by personal profit. Before Kennedy launched his own presidential campaign on a platform of “making America healthy again”, he earned $20,000 every week helming a non-profit dedicated to fostering vaccine skepticism. Now in the cabinet, he has fired the entire CDC vaccine advisory panel and replaced them with a ragtag crew, half of whom have never published peer-reviewed research on vaccines. Just last week, Kennedy cancelled $500m of federal funding for mRNA vaccines, which prevented 14m deaths during the Covid-19 pandemic. And he has made these rollbacks while retaining a financial stake in ongoing litigation against a vaccine manufacturer.

All the while, the US has seen more than 1,300 measles cases and three deaths this year. In response, Kennedy has alternately endorsed and undermined the most effective method of prevention – widespread immunization.

The evisceration of funding has extended across the sciences, with Trump cutting support for research to a 35-year nadir. At the National Institutes of Health, 1,800 grants have been terminated, a move that the Government Accountability Office deemed illegal. The administration also continues to freeze grants to universities over culture war phantasms like DEI, including $339m at UCLA and $2.2bn at Harvard. So it’s not surprising that 75% of US scientists polled by the journal Nature are considering leaving the country, which raises the prospect of a lost generation of American talent and lifesaving innovation.

Internationally, Trump’s heartless and thoughtless budget cuts are causing devastation. The administration has dismantled USAID, one of the most successful preventers of contagious disease in history. In doing so, it defunded programs that vaccinated more than 800 million children against fatal illnesses like malaria. Researchers have found that 300,000 people have already died because of these cuts, which could lead to another 14m preventable deaths over the next five years – all to gut an agency that managed the equivalent of 4% of the annual national defense budget.

Back in the US, medical associations, local officials and individual doctors are collaborating to buy vaccines directly from manufacturers and lobbying insurance companies to continue covering the costs of those shots. Their efforts reflect a tried-and-true strategy to counter under-immunization. Before the current outbreak, Ronald Reagan-era cuts to public health caused a more widespread measles pandemic, with 27,000 cases in just 1990. But locally led outreach campaigns and grassroots vaccination programs turned back the crisis, as did an eventual restoration of federal funds under Bill Clinton’s administration.

Budget cuts can be reversed, but trust may be more difficult to recover. Long before RFK Jr’s ascendancy, disasters like the CDC’s infamous Untreated Syphilis Study at Tuskegee and the Food and Drug Administration’s glacial response to the Aids crisis cast long shadows over public health institutions. Today, a plurality of Americans are already predicting they will lose faith in medical guidance under the current administration. That would undermine the very basis of public health, which depends on people choosing to follow guidelines grounded in research they did not personally conduct and whose results they are ill-trained to parse.

Repairing that breach will require years of effortful relationship-building, but it might also require rallying Americans with the classic tactic of patriotism. For all of Trump’s bellicose rhetoric, he misses that our nation’s most extraordinary scientific and medical advances have drawn bipartisan enthusiasm in part because they reinforced a perceived American exceptionalism. At the height of the cold war, RFK Jr’s uncle chose to go to the moon, and Richard Nixon brought that dream to fulfilment. After Franklin Delano Roosevelt founded the National Foundation for Infantile Paralysis, Americans helped fund it by mailing in more than 2.5m dimes, hence its christening as the March of Dimes. That money supported Jonas Salk’s development of the polio vaccine. Within two years of its introduction, annual cases of polio had fallen by 90%.

Even Trump, who botched the initial response to Covid-19, managed to oversee the historic Operation Warp Speed. If only he could recognize that this is the kind of achievement which makes America great.

The world’s largest conditional cash transfer programme, the Bolsa Família Programme (BFP), is associated with a substantial reduction in AIDS cases and deaths, especially among brown and black women with lower income and limited education. This was the main conclusion of a study coordinated by the Barcelona Institute for Global Health (ISGlobal), a centre supported by “la Caixa” Foundation, in collaboration with the National Institute of Allergy and Infectious Diseases (NAIDS/NIH). The results were published in Nature Human Behaviour.

Conditional cash transfer (CCT) programs, which provide financial aid to low-income households in exchange for fulfilling health and education requirements, are a key policy tool for addressing the social determinants of health. Implemented in nearly all low- and middle-income countries, CCTs aim to improve the living conditions of families in vulnerable situations.

Education amplifies the impact of conditional cash transfer programmes

“We analyzed data from 2007 to 2015, focusing on mothers and daughters in households receiving Bolsa Família, using a causal inference framework and a robust quasi-experimental design,” explains Andréa F. Silva, PhD in the Institute of Collective Health, Federal University of Bahia (UFBA) (Salvador, Brazil) and lead author of the study. The analysis covered 12.3 million low-income women, and explored how intersecting vulnerabilities – such as poverty, race, and education – affected the programme’s effectiveness.

Among daughters, the programme was associated with a 47% reduction in AIDS incidence and a 55% reduction in AIDS-related mortality. Among mothers, the reductions were 42% and 43%, respectively.

The programme’s impact was particularly significant among women facing multiple intersecting vulnerabilities. In particular, brown or black mothers living in extreme poverty and with higher levels of education experienced the greatest improvements: a 56% reduction in AIDS incidence. These findings suggest that education enhances the protective effects of cash transfers on health outcomes.

How Brazil is successfully reducing AIDS cases

Brazil has already reported a national decline in AIDS, with the relative incidence dropping by nearly 30% from 2007 to 2021, and over 40% among women. This study suggests that the BFP may be one of the reasons for this success, highlighting the importance of integrated social and health policy approaches.

Beyond financial aid, the BFP includes health and education conditionalities, such as mandatory school attendance, routine health checkups, and participation in health education activities, including sexual and reproductive health, which may further support HIV prevention and treatment. By improving nutrition, reducing food insecurity, and encouraging early engagement with healthcare services, these conditions create a multi-pronged approach to disease prevention.

This is the first large-scale study to assess the intersectional effectiveness of cash transfer programmes on HIV/AIDS outcomes. By linking massive socioeconomic and health datasets, the researchers were able to evaluate the effects of the Bolsa Família Programme across diverse subpopulations, many of whom are often underrepresented in traditional epidemiological studies or clinical trials. This is particularly relevant in policy evaluation: public interventions could have a very different impact according to the characteristics and baseline conditions, and of its beneficiaries.

In the current global context of increasing inequalities and poverty rates, CCT programmes have the potential to significantly reduce morbidity and mortality from AIDS, especially among populations with multiple vulnerabilities. Our findings show that these programmes not only reduce HIV risks and AIDS-related deaths, but also support progress toward the Sustainable Development Goals in Brazil and beyond.”

Davide Rasella, ICREA researcher at ISGlobal and coordinator of the study

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An infusion in the morning versus the afternoon. That’s it. Yet this simple difference translated into a median progression-free survival (PFS) of 11.3 months versus 5.7 months for patients with non-small-cell lung cancer (NSCLC) receiving immunochemotherapy.¹

When this data emerged from the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, it wasn’t just another clinical finding to file away – it challenged fundamental assumptions about what drives treatment outcomes in precision medicine.

The timing discovery: precision medicine’s unexpected result
These findings came from a phase 3 study of patients with advanced NSCLC receiving chemotherapy plus immunotherapy, randomised to receive their infusion either before or after 15:00. This simple timing switch led to a difference in PFS of 5.6 months, favouring patients receiving the earlier infusion.¹

An effect size of this magnitude rivals those seen with other precision medicine contenders. After all, that same ASCO congress delivered the wins we expected: Zipalertinib hit a 35% response rate in patients with EGFR exon 20 mutations in the phase 2b REZILIENT1 study – exactly the kind of biomarker-driven success that validates our molecular targeting approach in patients progressing after platinum-based chemotherapy.² Tarlatamab, a DLL3-targeting bispecific T-cell engager (BiTE), extended overall survival from 8.3 to 13.6 months versus chemotherapy in relapsed small-cell lung cancer (DeLLphi-304), another victory for targeted therapy.³

Preparing for the unpredictable
The ‘why’ behind the circadian effect is still unclear – the role of ‘clock’ genes in modulating immune system functional patterns is only beginning to be unpicked, but the precise mechanisms regarding timing of infusions are still vague.⁴

For pharma and medical communications professionals, this discovery exposes an uncomfortable truth. We’ve built entire scientific strategies around the assumption that we understand why our treatments work. But what happens when breakthroughs arise from factors we previously never thought to question – let alone measure?

The traditional approach – project confidence, avoid uncertainty – breaks down when impressive clinical data comes from unexpected variables. How do we create scientific strategies around the idea that ‘your appointment time might matter as much as your genetics’, even when we can’t predict which factors will surprise us next? Honesty is, perhaps, the most confident route of all.

Building what we don’t know into strategy
Most medical communications avoid uncertainty like the plague. But the circadian discovery suggests a different map for the road ahead: what if acknowledging the limits of current knowledge became a differentiator rather than a liability?

The organisations that will lead in precision medicine communications are those that prepare for discoveries they can’t predict. And with the pace of research and data generation increasing each year, there will inevitably be more. Take heart – there’s no need to overhaul messaging; instead, forward-thinking teams are building three core content approaches:

1. Modular content frameworks that can rapidly integrate new science without starting from scratch. Instead of traditional campaign materials, these are content systems designed for evolution – educational slides with flexible sections for emerging data, clinical summaries that can accommodate both molecular and non-molecular factors, patient materials with ‘discovery zones’ for unexpected findings.
2. Scenario planning for communications that goes beyond standard strategic planning. Rather than delivering a single communications strategy, sophisticated teams develop multiple strategic scenarios: what if environmental factors become as important as biomarkers? What if resistance patterns reshape treatment sequencing? What if simple interventions outperform complex ones? This approach transforms reactive scrambling into proactive preparation.
3. Evolution narratives that position unexpected discoveries as evidence of scientific progress rather than narrative disruption. When the next circadian timing-type breakthrough emerges, teams with evolution narratives already have frameworks to integrate it seamlessly into existing therapeutic stories.

In short, no more ‘by implementing these biomarker-driven strategies, we achieve optimal patient outcomes’ That sentence says nothing while pretending to say everything.

Instead, use scientific strategies that acknowledge the elephants in the room: ‘We know molecular targeting works. We’re learning that timing matters too. Environmental factors are proving significant. We’re probably missing other variables entirely.’

The communications teams that thrive will be those that view each unexpected discovery not as a threat to existing narratives, but as validation that the field is advancing faster than anyone predicted. Because in precision medicine for oncology, the only certainty is that we still have a lot to learn.

References:

1. Zhang Y, et al. J Clin Oncol. 2025;43(16_suppl):8516. doi:10.1200/JCO.2025.43.16_suppl.8516
2. Vu HA, et al. J Clin Oncol. 2025;43(16_suppl):8503. doi:10.1200/JCO.2025.43.16_suppl.8503
3. Rudin CM, et al. J Clin Oncol. 2025;43(17_suppl):LBA8008. doi:10.1200/JCO.2025.43.17_suppl.LBA8008
4. Karaboué A, et al. Br J Cancer. 2024;131:783–96

This thought leadership piece appeared in the July/August edition of PME. Read the full issue here

Missed abortion is a specific miscarriage subtype characterized by embryonic or fetal death without the natural expulsion of intrauterine products of conception [8, 11]. A variety of etiological factors, including maternal endocrine or immune-related factors, infections, abnormal thrombotic activity, fetal chromosomal abnormalities, and environmental influences, have been identified as contributing to missed abortion [12,13,14]. PCOS, one of the most common endocrine disorders in women of reproductive age [15, 16], has been shown to increase the risk of missed abortion [15, 16]. The results of the present study investigating the link between PCOS and missed abortion provide evidence that oligomenorrhea, menstrual period duration, and total testosterone are independent risk factors for missed abortion in women with PCOS.

The clinical presentation of PCOS is highly heterogeneous. According to the Rotterdam criteria, PCOS patients often experience oligomenorrhea or amenorrhea, although some may have regular menstrual cycles [10, 16, 17]. Menstrual irregularities in PCOS are primarily driven by insulin resistance and hyperandrogenism [18, 19]. While earlier studies suggested that menstrual patterns in PCOS patients are not independent risk factors for miscarriage [20], other research has demonstrated that early pregnancy loss in PCOS is closely linked to elevated androgen levels and insulin resistance [3, 21]. For example, a systematic review identified insulin resistance as a risk factor for spontaneous abortion in PCOS patients undergoing assisted reproductive treatment [21]. Hyperandrogenism has been shown to impair endometrial receptivity by thickening the endometrial subepithelial stroma and myometrium, thereby contributing to recurrent pregnancy loss [22]. Despite the extensive focus on miscarriage in women with PCOS, research on its association with missed abortion has been limited. This study addresses this gap by analyzing the relationship between PCOS and missed abortion, identifying oligomenorrhea and menstrual period duration as independent risk factors for this complication.

However, it is important to note that the absolute difference in menstrual period duration between the missed abortion and control groups was relatively small (approximately half a day). This minor discrepancy suggests that while menstrual period duration may correlate with missed abortion risk in statistical terms, its clinical relevance as an independent predictor is likely limited. It may reflect underlying hormonal imbalances (e.g., subtle perturbations in progesterone or estrogen dynamics) that are secondary to more impactful factors like ovulatory dysfunction (oligomenorrhea) or hyperandrogenism, rather than exerting a direct causal effect on pregnancy loss.

Infertility in PCOS is often attributed to ovulation irregularities, as well as endocrine and metabolic disorders, with assisted reproductive technology (ART) playing a pivotal role in achieving pregnancy for many affected women [23]. Notably, our study found that ART is not a significant risk factor for missed abortion in women with PCOS, a finding that may stem from differences in hormonal profiles—for example, a retrospective cohort study of 4,083 women undergoing IVF or ICSI revealed no significant differences in pregnancy loss or perinatal complications between PCOS patients without hyperandrogenism and controls [24]. This underscores the need to focus on endocrine-metabolic factors during ART interventions, as our analysis of these parameters further revealed key insights: total testosterone is an independent risk factor for missed abortion in PCOS, consistent with previous studies indicating that hyperandrogenism impairs endometrial receptivity and contributes to pregnancy loss [22, 25]. Meanwhile, AMH emerged as a risk factor in univariate analysis but not in multivariate models, suggesting its association with missed abortion is likely mediated by other factors such as hyperandrogenism [26, 27] rather than being an independent predictor. Although fasting insulin levels showed significant differences in descriptive statistics, they were not identified as a risk factor in either analysis, possibly due to the interplay between insulin resistance and hyperandrogenism—since androgens can drive insulin resistance in PCOS [28], the influence of fasting insulin may be overshadowed by the more prominent role of testosterone. Collectively, these findings highlight the importance of monitoring and regulating androgen levels, alongside addressing insulin resistance, during ART and broader clinical management of PCOS patients to reduce the risk of missed abortion.

These findings have practical implications for clinical practice: Clinicians should monitor menstrual patterns (especially oligomenorrhea) and measure testosterone levels in PCOS patients during preconception and early pregnancy. For those with oligomenorrhea or elevated testosterone, targeted interventions like ovulation induction or anti-androgen therapy may help reduce missed abortion risk, supporting personalized care to improve pregnancy outcomes.

This study has certain limitations. Due to the small sample size, some variables (e.g., conception method, occupation) were grouped into broader categories, which may have reduced data granularity. Additionally, as a retrospective study, it lacks data on potential biological risk factors such as oxidative stress and thrombophilia—factors known to affect PCOS pathophysiology and pregnancy outcomes, a gap to be considered when interpreting the findings. Future prospective studies with comprehensive biochemical and molecular profiling are needed to validate these results and explore how epidemiological factors interact with biological markers in predicting missed abortion in PCOS. While the between-group difference in menstrual period duration was statistically significant, the absolute difference was small (approximately half a day), limiting its practical relevance for clinical decision-making. Larger-sample studies with more detailed assessments of menstrual characteristics are thus required to clarify whether such subtle differences hold biological significance for predicting missed abortion risk in PCOS. Large-scale, multicenter prospective studies are recommended to further validate these findings.