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Infectious Diseases

Cytomegalovirus

Cytomegalovirus, or CMV, is a virus that is commonly transmitted in childhood and early adulthood. Approximately 60% of the U.S. population has been exposed and is latently infected. Worldwide data indicate that half the people in industrialized countries and up to 99% of people in developing countries, including China and India, have been infected.

Infections typically result in lifelong latent persistence of the virus with few symptoms, if any. However, in unborn children, when infected in utero, CMV infection can lead to significant morbidity and mortality.

In addition, in immunosuppressed patients, such as transplant recipients, primary CMV infection or reactivation of CMV causes significant morbidity, mortality and graft rejection. There are two scenarios in which CMV infections are relevant in the transplant setting. In one case, the recipient could be CMV negative, or previously uninfected, and the donor CMV positive. In this case, introduction of CMV into the immunocompromised recipient can lead to rapid virus spread and development of serious complications. In the other case, the recipient is already CMV positive, but the immunosuppressive treatments required as part of the transplant procedure lead to reactivation of latent virus.

Cytomegalovirus in Kidney Transplant Patients

High risk kidney transplant recipients are defined as CMV-negative patients receiving an organ from a CMV-positive donor. In this patient population, approximately 80% develop active CMV infection. But also, CMV-positive individuals undergoing kidney transplantation are at risk of clinically significant CMV infection/reactivation (approximately 40%). For this population, the level of T cell immunity prior to transplantation is predictive of the likelihood that they will develop CMV disease after transplantation.

Our solution: HB-101

HB-101 (ClinicalTrials.gov Identifier: NCT03629080) is a non-replicating product candidate designed to stimulate the immune system against Cytomegalovirus (CMV) and to protect against future CMV infection or reactivation from latency. HB-101 is comprised of two non-replicating LCMV-based vectors:

  • one vector expresses the gene encoding the CMV 65 kD pp65 protein, a validated T cell antigen; and
  • another vector expresses the gene encoding the CMV gB protein, a validated B cell / antibody target.

In 2018, we commenced a Phase 2 clinical trial for HB-101 in Cytomegalovirus-negative patients awaiting kidney transplantation from living Cytomegalovirus-positive donors. We added a new cohort of CMV-positive recipients awaiting kidney transplantation from CMV-positive or -negative donors to the trial protocol in early 2020.  We concluded enrollment of the ongoing Phase 2 trial in mid-2021 and will report final data in the first half of 2023. 

 

Hepatitis B Virus

An estimated 292 million people are living with HBV infection (defined as hepatitis B surface antigen positive). According to the WHO, HBV results in up to 1 million annual deaths globally, mostly from complications including liver cirrhosis and hepatocellular carcinoma. HBV virus is especially common in China and other Asian countries where mother-to-child transmission is an important source of transmission of the virus. HBV is second only to tobacco as a cancer-causing agent.

Our solution: HBV Therapy
The objective of the Hepatitis B virus (HBV) Program is to utilize the HOOKIPA Technologies to design arenavirus vectors (Lymphocytic Choriomeningitis Virus or Pichinde Virus based) suitable for treatment, cure or prevention of HBV. Together with our partner Gilead Sciences, we intend to develop functional therapies for patients already infected with HBV.

HOOKIPA has completed all of the required preclinical work on the HBV program, and Gilead intends to dose the first subject in a Phase 1 study in 2023.  HOOKIPA does not control the clinical timetable of the HBV therapy clinical program.

 

Human Immunodeficiency Virus (HIV)

Today, HIV continues to be a major global public health issue, having claimed more than 35 million lives so far and affecting approximately 36.9 million people at the end of 2017. HIV research has come a long way since the discovery of the disease in the 1980’s but there is no cure for HIV infection. There are antiretroviral (ARV) drugs that control the virus and help prevent transmission. The goal now is to find a cure for HIV to change the lives of millions affected by the disease.

Our solution: HIV Therapy
The objective of the Human Immunodeficiency Virus (HIV) program is to use HOOKIPA’s technologies to design arenavirus vectors (Lymphocytic Choriomeningitis Virus or Pichinde Virus based) suitable for treatment, cure or prevention of HIV. Together with our partner Gilead Sciences, we intend to develop functional therapies for patients already infected with HIV.

In February 2022, HOOKIPA and Gilead agreed to advance its partnered HIV program, triggering a $54 million commitment from Gilead. HOOKIPA assumed development responsibility for the HB-500 program through the completion of a Phase 1b clinical trial; Gilead has the exclusive right for further development thereafter. Financial terms included a $4 million preclinical milestone, a $15 million non-refundable initiation fee and $35 million equity commitment at a premium to market price.  If Gilead pursues further development, HOOKIPA is entitled to potential development and sales milestone payments exceeding $237 million, as well as royalties on net product sales.

The research phase of the HIV program has been completed, and the program is now in clinical development.  HOOKIPA aims to file the HIV program IND in 2023.