OTTAWA, Ontario, March 28, 2019 (Newswire.com) – Orion Biotechnology Canada Ltd., today announced that it will be presenting data on the potency of OB-002, their CCR5 antagonist currently in development for HIV prevention and oncology indications, at the 10th IAS HIV Science Meeting that will be held in Mexico City in July 2019.
OB-002 is an analogue of RANTES/CCL5, one of the ligands of the CCR5 HIV co-receptor. The CCR5 co-receptor plays a critical role in HIV infection. Individuals who are homozygous for a null nutation in the CCR5 receptor gene are highly resistant to HIV infection and blockade of the CCR5 receptor with CCR5 antagonists such as maraviroc has been used for the treatment and prevention of HIV infection. Topical OB-002 is highly effective in preventing vaginal transmission of SHIV1623P in a non-human primate (NHP) model of HIV infection (Veazey et al. JID 2009). In contrast, data for maraviroc has been more variable. Oral MVC did not protect NHPs from rectal SHIV1623P challenge (Massud et al. J Virol 2013) but topical MVC was protective in a vaginal challenge humanized mouse model (Neff et al. PLoS ONE 2011).
To further evaluate these differences in CCR5 anatagonist efficacy, inhibitory potency of a series of CCR5 antagonists were compared in (i) an HIV replication assay provided by ImQuest (http://imquestbio.com) using CCR5-tropic HIV BaL strain with PBMC from 18 different healthy donors and (ii) an aequorin-based functional inhibition assay provided by Euroscreen Fast (https://euroscreenfast.com). These studies will be critical in defining the in vitro activity of OB-002 as compared to other CCR5 antagonists and provide support for Phase 1 rectal and vaginal safety studies of Orion’s OB-002H microbicide gel which are planned to start in Q3 2019. They may also help explain the differences in efficacy between OB-002 and maraviroc in animal models of viral challenge.
“More detailed comparison of the in vitro CCR5 antagonist activity of OB-002 with other CCR5 inhibitors being developed for the treatment and prevention of HIV infection is a critical step in moving forward with the development of a safe and effective microbicide,” said Dr. Ian McGowan, Chief Medical Officer for Orion Biotechnology.
“Generation of these in vitro data are clearly very important for our microbicide development program but they will also provide valuable insights into the role of OB-002 as a potential immuno-oncology agent for the management of advanced cancer,” added Mark Groper, CEO at Orion Biotechnology.
OB-002 is a chemokine analogue, a new class of drug being developed by Orion Biotechnology. A novel recombinant protein product, OB-002 consists of a 69-residue analogue of the human chemokine protein RANTES/CCL5. OB-002 blocks CCR5, a cellular receptor interaction that plays an important role in HIV infection, tumor metastasis, neuroinflammation, and stroke recovery. Preclinical studies have demonstrated that OB-002 potently blocks the CCR5 receptor, has an excellent safety profile, and does not induce immune activation.
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