New focus on viral respiratory infections especially highly transmissible RSV
NanoViricides (NYSE-A:NNVC) (NV), a US company, owns a novel, multi-target, oral anti-viral platform that has completed its first clinical study. The development pathway is now being focused on general viral respiratory disease in India and on Respiratory Syncytial Virus lung infection in the US. The successful completion of Phase 1 healthy participant dosing with no adverse events was a key milestone; we expect the technical data from late summer onwards. There remains a need across many viral diseases for effective therapies. If, as preclinical data indicates, the candidate, anti-viral NV-387, can be delivered orally at effective doses against multiple respiratory viruses, including potentially Influenza A, RSV and COVID-19, it could become a mass market product. It might be prescribed by primary care physicians adding a new, acute therapeutic category to the RSV vaccine and antibody market already worth about US$3 billion.
NV had US3.25mln of cash on March 31. Management has stated that this is not sufficient to fund NV till March 2025. However, the company has access to further cash, has solid assets, and is seeking further funds or secured loans.
The putative COVID-19 therapy, NV-CoV-2 Phase I, containing NV-387, completed dosing of the 36 healthy participants in both single-dose (Phase 1a) and multiple-dose arms (Phase 1b). Participants received either a syrup or a gummy containing the anti-viral agent NV-387. A next stage was planned in mild-moderate COVID-19 patients. However, patients are now hard to recruit so this stage has closed. Hence, we do not see further development of a COVID-19 indication in India.
As preclinical work shows that NV-387 is effective against influenza and RSV viruses, a general anti-viral first response oral therapy against “Severe Acute Respiratory Infection”-Viral (SARI-Viral) might be feasible. Currently, this is not a recognized class of anti-viral and an appropriate clinical development strategy needs to be agreed with Indian regulators. The market is an attractive option.
In the US, the focus is on RSV. RSV is a viral lower lung infection particularly dangerous to infants under six months and young children up to five years old. It can also be dangerous in older adults (over 60), though they can be vaccinated where children cannot (although maternal vaccination during pregnancy is available to protect new born and young infants).
To enter US development, NV needs a pre-IND meeting with the FDA, probably once the Indian Phase 1 technical data is available and analyzed. This could be late summer 2024, and could enable an IND to be filed in Q1 2025 and granted by spring the same year. A Phase 2 could then run over the 2025-26 winter RSV season; RSV infections are highly seasonal (see below).
We also note excellent preclinical data on Influenza A treatment with NV-387 compared to existing blockbuster therapies.
Financial – material cash uncertainty
NanoViricides (NYSE-A:NNVC)’ 2023 accounts (10k) to June 30, 2023 showed cash (including prepayments) of US$8.46mln, down from $14.42mln in June 2022. In the accounts for the nine months to March 31, 2024, NV showed cash of $ 3.5mln (including prepayments). The cash burn, on average is US$1.6mln per quarter indicating about $2mln at the FY24 year end on June 30, 2024. There are some clinical trial payments and there will be Q3FY25 data processing and FDA regulatory costs. Given up to US$2mln Y/E cash and possible FY25 burn of at least $6-7mln, NV could need a at least US$4mln further in FY25 before any further trial costs.
A US RSV study has been roughly estimated to cost up to US5mln which would mostly be additional to the above but would, we understand, mostly be incurred in FY26 . Note that no US trial designs or costs can be clarified before the FDA pre-IND meeting so will not be clear till mid FY25 (late 2024). Any Indian SARI-Viral trial is still unclear but costs could be lower.
Accordingly, management has stated in the Q3FY24 report that current cash is not sufficient to fund the company for a further 12 months. NV has a line of credit from the CEO for up to US$2mln and is seeking to mortgage its headquarters, laboratory and GMP facility. An ATM facility for US$5.7mln was entered in August 2023 and became active in April 2024 which could yield cash if the market allows.
In our tentative financial forecasts, we have assumed careful cost control and added some extra US trial costs with an assumption of a further US5mln of funding plus the US$2mln CEO loan. The current market capitalization of about US$24mln would allow further funding.
NV announced more preclinical data on RSV on 14 May. The reported experiment compared oral ribavirin (as noted an off-label route in RSV) against oral NV-387. Mice infected with high RSV doses lived eight days if untreated, on average 14 with oral ribavirin and over 22 days on average (the end date of the experiment), hence indicating survival, with oral NV-387 (exhibit 2). Clearly, at the doses used (undisclosed) this is a major efficacy gain. It argues for a clinical trial.
Ribavirin is used orally to treat hepatitis C. It was approved in 1985 by the FDA as an inhaled formulation to treat severe RSV infection in children. It would normally be combined with other therapies. Oral doing is also used off label in adults. Adults undergoing chemotherapy or who have had stem cells transplants are particularly at risk of RSV.
Exhibit 1: RSV: mouse challenge model.
Dr Anil Diwan has been president and chairman since the company's founding in 2005. He invented novel polymeric micelle based nanomedicine technologies and founded TheraCour Pharma and AllExcel to develop the concept. TheraCour provides paid services to NanoViricides (NYSE-A:NNVC). He also founded Karveer Meditech in India. He has a doctorate from Rice University, Texas, and followed a career in the pharmaceutical industry. He is married to NanoViricides (NYSE-A:NNVC)' CFO Ms Vyas.
Preclinical tests show significant anti-RSV activity
Meeta Vyas, CFO, has both board and senior executive experience in a broad range of entities including publicly listed corporations, not-for profit and medium to large companies. Meeta has experience in performance and process improvement in finance and operations, strategy and management. She holds an MBA in finance from Columbia University and a BS in chemical engineering from MIT.
New preclinical data indicates wide spectrum NV-387 activity
NV has been developing the preclinical science of its micelle-based nanomedicine. The lead product is a sophisticated polymer (NV-387) to trap and disrupt viruses in the blood. The therapy aims to reduce the viral load to prevent infection of healthy cells and to enable the immune system to clear viruses rapidly. NV-387 has previously been observed to have preclinical “strong effectiveness” against RSV.
In new data (May 2024), NV has shown that NV-387 can be effective in a mouse model against Influenza A (H3N2). This model used a lethal dose of virus to get a clear effect in a short time. The data indicates a strong protective effect from NV-387. Fortunately, deaths from influenza are rare as a percentage of cases so mortality is not a good measure of a future clinical trial. Importantly, this used oral dosing (level undisclosed) which in this mass market is essential.
There are various existing therapies (Exhibit 2) but these need to be given early to have any effect. They typically reduce the duration of the symptoms by about 24 hours if taken within 48 hours of the infection starting. NV-387 increased survival by 88% compared to the control (called vehicle), Exhibit 2. Note that these preclinical experiments are very interesting but need translation into a human clinical context. Influenza trials tend to be large.
Preclinical Projects
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NV announced more preclinical data on RSV on 14 May. The reported experiment compared oral ribavirin (as noted an off-label route in RSV) against oral NV-387. Mice infected with high RSV doses lived eight days if untreated, on average 14 with oral ribavirin and over 22 days on average (the end date of the experiment), hence indicating survival, with oral NV-387 (exhibit 2). Clearly, at the doses used (undisclosed) this is a major efficacy gain. It argues for a clinical trial.
Ribavirin is used orally to treat hepatitis C. It was approved in 1985 by the FDA as an inhaled formulation to treat severe RSV infection in children. It would normally be combined with other therapies. Oral doing is also used off label in adults. Adults undergoing chemotherapy or who have had stem cells transplants are particularly at risk of RSV.
Exhibit 1: RSV: mouse challenge model.
Dr Anil Diwan has been president and chairman since the company's founding in 2005. He invented novel polymeric micelle based nanomedicine technologies and founded TheraCour Pharma and AllExcel to develop the concept. TheraCour provides paid services to Nanoviricides. He also founded Karveer Meditech in India. He has a doctorate from Rice University, Texas, and followed a career in the pharmaceutical industry. He is married to NanoViricides' CFO Ms Vyas.
Preclinical tests show significant anti-RSV activity
Meeta Vyas, CFO, has both board and senior executive experience in a broad range of entities including publicly listed corporations, not-for profit and medium to large companies. Meeta has experience in performance and process improvement in finance and operations, strategy and management. She holds an MBA in finance from Columbia University and a BS in chemical engineering from MIT.
New preclinical data indicates wide spectrum NV-387 activity
NV has been developing the preclinical science of its micelle-based nanomedicine. The lead product is a sophisticated polymer (NV-387) to trap and disrupt viruses in the blood. The therapy aims to reduce the viral load to prevent infection of healthy cells and to enable the immune system to clear viruses rapidly. NV-387 has previously been observed to have preclinical “strong effectiveness” against RSV.
In new data (May 2024), NV has shown that NV-387 can be effective in a mouse model against Influenza A (H3N2). This model used a lethal dose of virus to get a clear effect in a short time. The data indicates a strong protective effect from NV-387. Fortunately, deaths from influenza are rare as a percentage of cases so mortality is not a good measure of a future clinical trial. Importantly, this used oral dosing (level undisclosed) which in this mass market is essential.
There are various existing therapies (Exhibit 2) but these need to be given early to have any effect. They typically reduce the duration of the symptoms by about 24 hours if taken within 48 hours of the infection starting. NV-387 increased survival by 88% compared to the control (called vehicle), Exhibit 2. Note that these preclinical experiments are very interesting but need translation into a human clinical context. Influenza trials tend to be large.
Preclinical Projects
Preclinical tests show significant anti-RSV activity
NV announced more preclinical data on RSV on 14 May. The reported experiment compared oral ribavirin (as noted an off-label route in RSV) against oral NV-387. Mice infected with high RSV doses lived eight days if untreated, on average 14 with oral ribavirin and over 22 days on average (the end date of the experiment), hence indicating survival, with oral NV-387 (exhibit 2). Clearly, at the doses used (undisclosed) this is a major efficacy gain. It argues for a clinical trial.
Ribavirin is used orally to treat hepatitis C. It was approved in 1985 by the FDA as an inhaled formulation to treat severe RSV infection in children. It would normally be combined with other therapies. Oral doing is also used off label in adults. Adults undergoing chemotherapy or who have had stem cells transplants are particularly at risk of RSV.