Products

Overview

Antiva is developing ABI-2280, a novel, topical therapeutic for the treatment of oncogenic (high-risk) HPV infection and pre-cancerous moderate to high-grade cervical intraepithelial neoplasias (CIN 2,3) caused by HPV. ABI-2280 utilizes prodrug chemistry developed by Dr. Karl Hostetler at the University of California San Diego and is formulated as an intravaginal insert to be self-administered by the patient in the privacy of their home.

Antiva has completed a randomized, double-blind, placebo-controlled Phase 1b/2 study in women diagnosed with persistent high-risk cervical HPV infection. This study achieved its primary endpoint with patients receiving ABI-2280 demonstrating statistically significant improvements in the rate of hrHPV negativity at Week 12 as compared with placebo. Additionally, this trial showed ABI-2280 treatment to be safe and well tolerated with the most commonly reported adverse events categorized as mild and moderate and localized to the treatment area.

Antiva also has an ongoing open-label Phase 1b/2 study in HPV positive women with CIN 2,3 to evaluate the safety, tolerability and efficacy of ABI-2280 in treating hrHPV infection and clearing pre-cancerous cervical lesions in these patients.

High-risk HPV (hr HPV)

Genital HPV is the most common sexually transmitted infection (STI) in the United States and worldwide for both women and men. In the U.S., there are approximately 6 million new cervical HPV infections each year. It is so common that 80% of women will get at least one type of HPV at some point in their lifetime.

Sexually transmitted HPV types fall into two groups: low risk and high risk. High-risk HPVs can cause several types of cancer including cervical cancer. The development of cervical cancer typically follows a phase of persistent infection with high-risk HPV that arises due to a failure of the host immune system to effectively clear HPV-infected cells. Approximately 30 percent of women with HPV fail to clear the infection within 12 months. These patients are considered to have persistent high-risk HPV (hrHPV) and have an estimated 20 percent chance of having their infection progress to pre-cancer over the following four-to-six years.

There are currently no approved treatment options for high-risk HPV infection. Recommended treatment guidelines for diagnosed HPV infection is to “wait and see” if the infection resolves, persists, or progresses to pre-cancerous lesions or cancer of the cervix. During this “wait and see” period which can last for years, the patient will have numerous follow up visits with a health care provider which can be burdensome and costly. In addition, the patient would need to either abstain from sexual relations or risk transmitting this virus to sexual partners.

HPV infections and the disease states driven by such infections remain a major unmet clinical need due to low vaccine adoption rates in major territories such as the US, EU, and Japan, limited vaccine access in developing countries as well as incomplete coverage of the known oncogenic subtypes in the currently available HPV vaccines.

A topical intravaginal treatment that is effective in treating high-risk HPV infection would be beneficial in preventing progression of infection to CIN 2,3 and cervical cancer and protecting women from the psychological and social repercussions of having a sexually transmitted infection. HPV is also known to drive the formation of other cancers such as anal, penile, head and neck cancers. Thus, treating HPV infection could also reduce transmission and lower rates of other HPV-related cancers.

Cervical Cancer and CIN

Globally, cervical cancer is the fourth most common cancer in women and represents a major public health problem. In 2022, an estimated 660,000 women were diagnosed with cervical cancer worldwide and approximately 350,000 women died from the disease.1 In the U.S., >14,000 women are diagnosed annually with cervical cancer and another 300,000 women are diagnosed with pre-cancerous lesions (CIN 2,3).

The burden of cervical cancer is disproportionately in underserved populations due to lack of resources including HPV vaccination, HPV screening and treatment. In the U.S., Black women have the highest incidence and mortality of cervical cancer, followed closely by Hispanic women2; LGBT populations may also be at an increased risk due to fear of discrimination or negative experiences with the healthcare system3. In addition, for all races, both cervical cancer incidence and poorer outcomes are higher in rural populations4. This reflects barriers to screening, diagnosis, and treatment for CIN 2,3, due to poor access to clinics and shortage of gynecologists.

The current treatment guidelines for CIN 2,3 involve in-office surgical-based procedures which ablate or excise a portion of the cervix. The ablative and excisional options include cryotherapy, thermal ablation, laser therapy, loop electrosurgical excision procedure (LEEP) or cold knife conization (CKC); the latter two excisional procedures remove one to three centimeters of cervical tissue and permanently alter the architecture of the cervix. Although these surgeries are highly effective, 5–16% of people will have a recurrence of CIN 2,3 within 5 years of the procedure. In addition, these procedures can negatively impact reproductive health. Studies have shown that women having excisional removal of CIN 2,3 are 2 to 3 times more likely to have premature delivery than untreated women, with attendant lower birth weight, higher rates of NICU admission and perinatal mortality5.

A topical intravaginal treatment for CIN 2,3 that could be prescribed by general practitioners and self-administered by patients at home would improve access to treatment worldwide and decrease morbidity and mortality as well as providing women with a treatment option that does not compromise their reproductive health.

ABI-2280 Mechanism of Action

Antiva has applied its expertise in pro-drug chemistry and topical formulation to create ABI-2280, an acyclic nucleoside phosphonate prodrug of PMEG diphosphate, that can be self-administered topically as a vaginal insert and is rapidly taken up into epithelial cells achieving effective cervical concentrations while minimizing systemic exposures thereby limiting systemic toxicity.

ABI-2280 has a potent dual anti-proliferative and anti-viral mechanism of action and works by directly inhibiting human intracellular DNA polymerases used by all HPV types for viral replication. Inhibition of HPV-infected cell proliferation induces apoptosis of productively infected cells while sparing quiescent, HPV-uninfected normal cells.

Moreover, because ABI-2280 targets human DNA polymerases instead of a specific viral protein and demonstrates broad activity against diverse HPV subtypes it has the potential to treat all HPV subtypes globally. Furthermore, we expect ABI-2280 to be effective in all stages of HPV-associated disease as drug resistance should not occur as ABI-2280 does not target a specific HPV protein. As the mechanism of action of ABI-2280 is independent of the immune system it may also be effective in immunocompromised HIV-infected patients.

ABI-2280 Global Development for High-Risk HPV and CIN 2,3

ABI-2280 is being developed globally for two indications: high-risk cervical HPV infection and CIN 2,3. We have completed a Phase 1 clinical study to evaluate the safety, tolerability and pharmacokinetics of ABI-2280 in healthy volunteers. We have also completed a randomized, double-blind, placebo-controlled Phase 1b/2 study of ABI-2280 in women with persistent high-risk HPV infection and have an ongoing open-label Phase 1b/2 study in CIN 2,3 patients.

“Women with persistent high-risk HPV have an approximately one-in-five chance of their infection progressing to pre-cancer or worse over four-to-six years, yet they do not have any options to treat the infection in the hopes of halting disease progression before this occurs. This reality highlights the clinical importance of the data generated in this study of ABI-2280, which demonstrated a 30 percent improvement in hrHPV negativity as compared to placebo, combined with a favorable safety and tolerability profile.”

—Margaret Stanley, OBE, FMedSci, Hon FRCOG, FFPH

Professor Emeritus, University of Cambridge

  1. WHO. Cervix Uteri - Cancer Fact Sheet. Cancer Today 2024.  https://gco.iarc.who.int/media/globocan/factsheets/cancers/23-cervix-uteri-fact-sheet.pdf.
  2. Kaiser Family Foundation, Cervical Cancer Incidence Rate per 100,000 Women by Race/Ethnicity. KFF/State Health Facts, 2018.  https://www.kff.org/4d860fe/
  3. American Cancer Society, Cancer Facts for Lesbian and Bisexual Women. ACS/Cancer Facts: Prevention and Screening, 2021.  https://www.cancer.org/healthy/cancer-facts/cancer-facts-for-lesbian-and-bisexual-women.html
  4. ACOG, Committee Opinion No. 586: Health disparities in rural women. Obstet Gynecol, 2014 (Reaffirmed 2019). 123(2 Pt 1): p. 384-388.  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/02/health-disparities-in-rural-women
  5. Kyrgiou, M., et al., Obstetric outcomes after conservative treatment for cervical intraepithelial lesions and early invasive disease. Cochrane Database Syst Rev, 2017. 11(11): p. Cd012847.  https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012847/pdf/full