PepCan / University of Arkansas for Medical Sciences - LARVOL DELTA

Advances in Therapeutic Vaccines Against HPV: A Review of Human Clinical Trials. (PubMed, Curr Oncol) - "Seventeen clinical trials were identified, including DNA-based (VGX-3100, GX-188E), viral-vector (MVA E2, TG4001), peptide-based (Pepcan), and bacterial-vector (GLT 001) vaccines. Variability in study designs and endpoints underlines the need for standardized protocols and further phase III trials. Overall, therapeutic HPV vaccines represent a rapidly advancing field with the potential to complement prophylactic vaccination and screening, thereby strengthening global cervical cancer control efforts, particularly in LMICs."

Journal • Review • Cervical Cancer • Infectious Disease • Oncology • Solid Tumor

Multimodal profiling of Pepcan-CB1 receptor structure-activity relationships: integrating molecular dynamics simulations, biological profiling, and the deep learning model MuMoPepcan. (PubMed, Bioorg Chem) - "We validated our hypothesis on cannabinoid receptors type 1 (CB1) and pepcans: (1) In the study, we synthesized 45 pepcan peptides to establish a bioactivity dataset and identified RD-pepcan-11 as an lead analgesic compound by Bioscreening, with systematic characterization of its CB1 selectivity and pharmacodynamics.; (2) Millions of conformational data were generated by MDS and a CB1-pepcans conformation dataset was constructed; (3) Combining wet-lab data and MDS data, a deep learning model - MuMoPepcan was developed, reducing prediction errors to within the error range of wet-lab experiments. This study not only identified novel high-potential pepcans - RD-pepcan-11, but also demonstrated that MDS can serve as an effective data augmentation method to scale up drug-receptor datasets, thereby improving model generalizability and performance."

Journal • Pain

A Phase I/II Clinical Trial of PepCan in Head and Neck Cancer Patients (clinicaltrials.gov) - P1/2 | N=21 | Completed | Sponsor: University of Arkansas | Active, not recruiting ➔ Completed

Trial completion • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

CANDIDA-INDUCED HISTOLOGICAL REGRESSION OF CERVICAL INTRAEPITHELIAL NEOPLASIA 2/3 IS LIKELY MEDIATED THROUGH REDUCTION OF TUMOR-PROMOTING CYTOKINES (IPVC 2024) - P2 | "PepCan consists of four HPV 16 E6 peptides and a Candida skin testing reagent (Candin®, Nielsen Biosciences)... Administering immune-enhancing adjuvant alone is sufficient for inducing anti-HPV immune responses. Candida should be evaluated in a Phase 3 trial as a potential new treatment for CIN2/3 which works through reducing the tumor-promoting systemic mediators."

IO biomarker • Cervical Cancer • Gynecology • Oncology • IFNG • IL9

RECRUITMENT FOR AND RETENTION IN A PHASE I/II RANDOMIZED DOUBLE-BLIND CLINICAL TRIAL OF A HUMAN PAPILLOMAVIRUS THERAPEUTIC VACCINE, PEPCAN (IPVC 2024) - "Patients were primarily motivated by their health needs to participate in the study. The retention rate was high."

Clinical • P1/2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

MP-13, a novel chimeric peptide of morphiceptin and pepcan-9, produces potent antinociception with limited side effects. (PubMed, Neuropeptides) - "PERSPECTIVE: This article offers insights into the combination treatment of pepcans with morphiceptin. Among the chimeric peptides, MP-13 exhibited potent analgesic effects in a series of preclinical pain models with a favorable side-effect profile."

Adverse events • Journal • Addiction (Opioid and Alcohol) • Gastrointestinal Disorder • Pain

Immune responses in a phase 2 clinical trial of peptide-based therapeutic human papillomavirus vaccine, PepCan, versus Candida adjuvant alone in treating cervical intraepithelial neoplasia 2/3. (ASCO 2024) - P2 | "Therefore, exogenous HPV antigens were not necessary to induce anti-HPV T cell responses. Administration of immune-enhancing adjuvant alone is sufficient for inducing anti-HPV immune responses. Consistent systemic decrease in RANTES/CCL5 was demonstrated suggesting possible mechanism in which Candida works through reducing RANTES/CCL5."

Clinical • IO biomarker • P2 data • Cervical Cancer • Dermatology • Gynecology • Oncology • IL12A

A Phase I/II Clinical Trial of PepCan in Head and Neck Cancer Patients (clinicaltrials.gov) - P1/2 | N=21 | Active, not recruiting | Sponsor: University of Arkansas | Trial completion date: Jun 2026 ➔ Apr 2025 | Trial primary completion date: Dec 2025 ➔ Apr 2025

Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Phase I/II Clinical Trial of PepCan in Head and Neck Cancer Patients (clinicaltrials.gov) - P1/2 | N=21 | Active, not recruiting | Sponsor: University of Arkansas | Recruiting ➔ Active, not recruiting

Enrollment closed • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A peptide-based human papillomavirus therapeutic vaccine, PepCan, or Candida adjuvant alone in treatment of cervical intraepithelial neoplasia 2/3 (CIN2/3). (ASCO 2023) - P2 | "PepCan and Candida treatments are safe. Only Candida was effective in inducing histological regression in the intention-to-treat and per-protocol analyses. Candida could become a new treatment for CIN2/3 by eliciting general immune stimulation similar to checkpoint inhibitors."

Clinical • Dermatology • Gynecology • Oncology • IL12A

A RANDOMIZED DOUBLE-BLIND PHASE II CLINICAL TRIAL OF AN HPV THERAPEUTIC VACCINE, PEPCAN, AND CANDIDA ADJUVANT FOR TREATING CERVICAL INTRAEPITHELIAL NEOPLASIA 2/3 (CIN2/3) (IPVC 2023) - P2 | "Only Candida was effective in inducing histological regression in the intention-to-treat and per-protocol analyses. Candida alone could become a new treatment for CIN2/3, which can be administered by non-physicians."

Clinical • P2 data • Dermatology • Gynecology • Musculoskeletal Pain • Oncology • Pain • IL12A

A Clinical Trial of PepCan to Two Therapy Arms for Treating Cervical High-Grade Squamous Intraepithelial Lesions (clinicaltrials.gov) - P2 | N=99 | Completed | Sponsor: University of Arkansas | Active, not recruiting ➔ Completed | Trial completion date: Jun 2025 ➔ Sep 2022

Trial completion • Trial completion date • Gynecology • Oncology

A Clinical Trial of PepCan to Two Therapy Arms for Treating Cervical High-Grade Squamous Intraepithelial Lesions (clinicaltrials.gov) - P2 | N=125 | Active, not recruiting | Sponsor: University of Arkansas | Trial primary completion date: Jun 2022 ➔ Aug 2022

Trial primary completion date • Gynecology • Oncology

A Phase I/II Clinical Trial of PepCan in Head and Neck Cancer Patients (clinicaltrials.gov) - P1/2; N=20; Recruiting; Sponsor: University of Arkansas; Trial completion date: Dec 2021 ➔ Jun 2026; Trial primary completion date: Sep 2021 ➔ Dec 2025

Clinical • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Expansion of Human Papillomavirus-Specific T Cells in Periphery and Cervix in a Therapeutic Vaccine Recipient Whose Cervical High-Grade Squamous Intraepithelial Lesion Regressed. (PubMed, Front Immunol) - "We describe a woman who received a human papillomavirus (HPV) therapeutic vaccine called PepCan, and experienced complete resolution of her cervical high-grade squamous intraepithelial lesion...Combining traditional and cutting-edge immunomonitoring techniques enabled us to demonstrate expansion of HPV-antigen specific T cells not only in the periphery but also in the cervix. Such an approach should be useful as a novel approach to assess vaccine-specific responses in various anatomical areas."

Journal • Gynecology • Oncology • IFNG

A Clinical Trial of PepCan to Two Therapy Arms for Treating Cervical High-Grade Squamous Intraepithelial Lesions (clinicaltrials.gov) - P2; N=125; Active, not recruiting; Sponsor: University of Arkansas; Trial completion date: Sep 2021 ➔ Jun 2025; Trial primary completion date: Sep 2021 ➔ Jun 2022

Clinical • Trial completion date • Trial primary completion date • Gynecology • Oncology

A Clinical Trial of PepCan to Two Therapy Arms for Treating Cervical High-Grade Squamous Intraepithelial Lesions (clinicaltrials.gov) - P2; N=125; Active, not recruiting; Sponsor: University of Arkansas; Recruiting ➔ Active, not recruiting

Enrollment closed • Gynecology • Oncology

Characterization of pepcan-23 as pro-peptide of RVD-hemopressin (pepcan-12) and stability of hemopressins in mice. (PubMed, Adv Biol Regul) - "Overall, we show that pepcan-23 is a biological pro-peptide of RVD-hemopressin and divalent metal ions may regulate this process. Given the lack of metabolic stability of hemopressins, administration of pepcan-23 as pro-peptide may be suitable in pharmacological experiments as it is converted to RVD-hemopressin in vivo."

Journal • Preclinical

Hemopressin as a breakthrough for the cannabinoid field. (PubMed, Neuropharmacology) - "While hemopressin was shown to have inverse agonist/antagonistic activity, extended forms of hemopressin (i.e. RVD-hemopressin, also called pepcan-12) exhibit type 1 and type 2 cannabinoid receptor agonistic/allosteric activity, and recent studies suggest that they can activate intracellular mitochondrial cannabinoid receptors...In this article, we briefly review the molecular and behavioral pharmacological properties of hemopressins, and summarize studies on the intricate and unique mode of generation and binding of these peptides to cannabinoid receptors. Thus, the review provides a window into the current status of hemopressins in expanding the repertoire of signaling and activity by the endocannabinoid system, in addition to their new potential for pharmaceutic formulations."

Journal • Review • CNS Disorders • Epilepsy • Immunology • Inflammation • Multiple Sclerosis • Oncology • Pain

A Clinical Trial of PepCan to Two Therapy Arms for Treating Cervical High-Grade Squamous Intraepithelial Lesions (clinicaltrials.gov) - P2; N=125; Recruiting; Sponsor: University of Arkansas; Trial completion date: Aug 2020 ➔ Aug 2021; Trial primary completion date: Aug 2020 ➔ Aug 2021

Clinical • Trial completion date • Trial primary completion date • Gynecology • Oncology

[VIRTUAL] IDENTIFYING ACTIVE COMPONENTS OF CANDIDA SKIN TEST REAGENT USED AS AN ADJUVANT IN AN HPV THERAPEUTIC VACCINE, PEPCAN (IPVC-I 2020) - "Cytokine analysis revealed that the most number of significant increases (6 cytokines) occurred in the same fraction containing A. Conclusions The fraction containing A appears to be most biologically active. Future study would involve identification of this molecule, and a confirmation of its immunostimlulatory activities."

Clinical • CCL11 • CCL3 • CCL4 • CCL5 • CSF2 • CXCL8 • FGF • IFNG • IL10 • IL12A • IL13 • IL15 • IL17A • IL1B • IL1R1 • IL2 • IL4 • IL5 • IL6 • IL7 • IL9 • PCR • TNFA • VEGFA

Cervical Microbiome and Response to a Human Papillomavirus Therapeutic Vaccine for Treating High-Grade Cervical Squamous Intraepithelial Lesion. (PubMed, Integr Cancer Ther) - "PepCan is an investigational HPV therapeutic vaccine for treating cervical high-grade squamous intraepithelial lesions...Further analyses showed significant differences at the empirical Operational Taxonomic Unit level for race and HPV 16 status. As these results are from a small Phase I study, further studies are needed to examine the role of cervical microbiome in response to HPV therapeutic vaccines."

Journal • Cervical Cancer • Gynecologic Cancers • Immunology • Infectious Disease • Oncology • Solid Tumor

A Phase I/II Clinical Trial of PepCan in Head and Neck Cancer Patients (clinicaltrials.gov) - P1/2; N=20; Recruiting; Sponsor: University of Arkansas; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open