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Overview

Antiva is developing ABI-2280, a novel, topical therapeutic for the treatment of persistent high-risk HPV infection and pre-cancerous moderate to high-grade cervical intraepithelial neoplasias (CIN 2,3) caused by HPV, before they progress to invasive cervical cancer. ABI-2280 utilizes lipophilic 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 is currently enrolling a randomized, controlled Phase 1b/2 study in women with persistent high-risk HPV infection and an open-label Phase 1b/2 study in women with CIN 2,3.

High-risk HPV (hr HPV)

Genital HPV is the most common sexually transmitted infection (STI) in the United States and globally for both women and men. In the U.S., >5.5M women are diagnosed annually with HPV infection. 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. Of the 12 high-risk HPV types associated with cervical cancer two particular types, HPV 16 and HPV 18, are responsible for most HPV-related cervical cancers. 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.

There is no approved treatment for high-risk HPV infection. Current 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.

A topical intravaginal treatment that is effective in treating persistent 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 cone (CKC); the latter two excisional procedures remove one to three centimeters of cervical tissue. 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 lipophilic pro-drug chemistry and topical formulation to create ABI-2280, an acyclic nucleoside phosphonate prodrug of PMEG diphosphate, that can be self-administered topically and is rapidly taken up into epithelial cells but has no systemic bioavailability 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 and not 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: persistent high-risk 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. Based on the Phase 1 safety and tolerability of ABI-2280 we are currently enrolling a randomized, controlled Phase 1b/2 study in women with persistent high-risk HPV infection and an open-label Phase 1b/2 study in CIN 2,3 patients.

“Worldwide there are more than 500,000 new cases and 300,000 deaths attributed to cervical cancer each year. This is a staggering statistic and especially tragic as there is no question that cervical cancer is a preventable disease. With a coordinated global program of vaccination, screening and treatment, cervical cancer can and should be eliminated within a generation. As a clinician, I see each case of cervical cancer as a failure on the part of the healthcare system and look forward to a time when we can claim more successes.”

—Catherine Behrens, MD, PhD, FACOG

Clinician and clinical scientist with expertise in HPV-related diseases

  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