Clinical-stage biopharmaceutical company Immunic Inc. has signed an in-license agreement with the University Medical Center Goettingen, Germany, covering the combination of DHODH inhibitors and nucleoside analogues to treat viral infections (COVID-19 and Influenza). Terms of the agreement were not disclosed.
 

Inhibiting SARS-CoV-2 Replication 
 

Preclinical research recently completed by the parties and their collaborators has shown that certain DHODH inhibitors, including Immunic’s lead asset, IMU-838, strongly synergize with selected nucleoside analogues to inhibit SARS-CoV-2 replication in vitro.
 
For instance, in an in vitro test system, IMU-838 alone showed an up to 99.9% reduction in viral RNA at concentrations of 5 μM, which is well within the exposure levels seen in prior clinical trials. Likewise, N4-hydroxycytidine (NHC), the active metabolite of molnupiravir, alone, was associated with an up to 99% reduction in viral RNA at concentrations of 100 nM. Compared to single agent activity, the combination of IMU-838 and NHC achieved an extra-ordinary reduction in viral RNA, down to the limit of detection, reducing SARS-CoV-2 RNA by up to seven log units (corresponding to 0.00001% viral RNA remaining). This powerful reduction of virus replication in vitro was demonstrated across multiple SARS-CoV-2 variants, including alpha, beta and delta, highlighting the independence of this approach to mutant virus forms. In addition to molnupiravir, Immunic is exploring alternate nucleoside analogues, some of which have shown very promising antiviral activity in vitro. The company plans to present detailed data at an upcoming scientific conference.
 
“Research by the University Medical Center Goettingen and other research partners revealed a profound degree of synergy in vitro when combining certain nucleoside analogues with DHODH inhibitors, including both our lead asset IMU-838 and other of our preclinical molecules,” stated Daniel Vitt, Ph.D., chief executive officer and president of Immunic. “Recalling IMU-838’s clinical activity against COVID-19 in our phase 2 CALVID-1 trial published earlier this year, and in light of recent exacerbations in COVID-19, worldwide, we are very excited to have in-licensed this technology to incorporate into our pandemic preparedness effort. However, with the extra-ordinary wealth of activity already ongoing at the company in other programs, we intend to evaluate and pursue the best possible strategic option for this program, including potential partnership, collaboration or external funding.”
 
The company says phase 2 top-line data of IMU-838 in ulcerative colitis is expected to be available in the second quarter of 2022, and that regarding IMU-935, data from the multiple ascending dose part of the ongoing phase 1 trial is expected in the fourth quarter of 2021, with initial clinical data in psoriasis expected in the second quarter of 2022. The phase 1 trial of IMU-935 in metastatic castration-resistant prostate cancer is expected to commence in the fourth quarter of 2021.
 
Moreover, the company continues to expect enrollment of the first patient in the phase 2 CALLIPER trial of IMU-838 in progressive multiple sclerosis later this month, and first patient in the phase 3 ENSURE program of IMU-838 in relapsing-remitting multiple sclerosis in the fourth quarter of 2021.
 
Hella Kohlhof, Ph.D., chief scientific officer of Immunic, commented, “We are very excited to see this remarkable synergistic antiviral activity, particularly as it is found well within exposure levels for IMU-838 in humans, associated with an extremely favorable safety profile. In addition to IMU-838, we also have a number of preclinical compounds that we believe are worth pursuing here, and we look forward to further refining potential combinations and compounds, with the goal of improving on the already strong antiviral activity demonstrated by IMU-838 alone in the clinic.”
 
Matthias Dobbelstein, M.D., professor of Molecular Oncology, University Medical Center Goettingen, added, “We are proud of the results of our preclinical work. These results identify a potential therapeutic strategy to inhibit the replication of SARS-CoV-2 in infected individuals. The synergistic antiviral effects of these combinations were astounding, and we are not aware of any other approaches which match this level of synergy against coronaviruses in vitro. We were very pleased with this license agreement with Immunic and look forward to future results with these very promising combinations.”