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Paving the way
SHELTON, Conn.—NanoViricides Inc., a technology platform-based company focused on treating viral diseases, has moved its first drug candidate into IND-enabling safety/toxicology studies, with plans to begin human clinical trials for a broad-spectrum drug candidate it hopes to develop for the treatment of herpesviruses.
The drug candidate NV-HHV-101 employed for these non-clinical IND-enabling studies is one of several compounds in development as candidates against VZV, the virus that causes chickenpox in children and shingles in adults. Upon successful completion of the safety/toxicology studies, NanoViricides expects to advance NV-HHV-101 into human clinical trials for a topical dermal treatment of the shingles rash as its initial indication.
The drug candidate is a refined version of two related development candidates in the company’s HerpeCide program that were reported as safe in non-Good Laboratory Practice tolerability studies announced in April 2018.
“NV-HHV-101 is a small modification of these two related drug candidates,” says Dr. Anil Diwan, president and executive chairman of NanoViricides. “It is the drug candidate further optimized from those two leads and is selected for further clinical development. Those two candidates will remain as back-up candidates.”
According to a media release announcing the NV-HHV-101 IND-enabling studies, the company also expects two additional topical treatment candidates in their HerpeCide program to follow the shingles candidate into IND-enabling development and then into human clinical trials. These treatments are indicated for treating herpes simplex virus (HSV) types 1 (oral herpes) and 2 (genital herpes).
“Whichever model becomes available first—whether HSV-1 or HSV-2—it will enable us to begin optimization of the drug candidate for treatment of that viral disease,” Diwan comments. “We have developed multiple ligands as well as multiple polymer backbones along the way. However, we are planning to perform further optimization for the HSV-1 and HSV-2 using NV-HHV-101 as the starting point, so that we can utilize the safety-toxicology data generated while studying it as a drug against shingles, to the extent possible.”
“The nanoviricides technology is based on attacking the virus through several points of binding to the virus, thereby encircling it and dismantling it,” he continues. “The design of the backbone polymer is tailored to the route of administration, in this case dermal. The ligands for VZV were designed originally for HSV-1 and HSV-2, and were found to be effective against VZV in cell culture studies, as well as later in human skin patch studies.”
NanoViricides estimates that the potential market size for the combined suite of diseases caused by HSV-1, HSV-2 and VZV could exceed tens of billions of dollars. Diwan sees an unmet need for shingles treatments in immunocompromised patients, for whom the shingles vaccine Shingrix, introduced by GlaxoSmithKline in 2018, cannot be used. Healthcare providers may also seek alternatives to the vaccine because of the potential for side effects.
According to Diwan, “This vaccine has caused very severe side effects in 15 to 20 percent of the patients, causing loss of one or more work days. Given that shingles is not a lethal disease and its incidence rate is once in a lifetime for healthy persons, this side effects profile may stand in the way of substantial adoption of this vaccine.”
Oral medications currently on the market for treating shingles outbreaks also leave room for improvement, Diwan notes.
“Available treatments for shingles include oral antiviral medications based on nucleotide analogues (acyclovir, gancyclovir and famcyclovir). All of these have poor effectiveness because, unlike HSV-1 and HSV-2, the virus that causes shingles does not produce a good viral enzyme called TK, which is required to convert these drugs to active forms,” he explains. “In addition, very little of the orally taken drug presents itself in the small site of the infection, so the dosage of these oral drugs for shingles treatment is extremely high. Additionally, they are effective only if taken within the first 48 hours of the beginning of appearance of the shingles rash—this is almost always missed.”
“We anticipate that NV-HHV-101 should be substantially superior in viral load reduction as well as in pain reduction for the treatment of shingles; if successful, this would mean substantial superiority to existing treatments,” adds Diwan. “Additionally, it is non-toxic to the extent that we have been able to study it so far—the IND-enabling safety/toxicology studies have begun now. Therefore, it can be applied as needed to provide substantial relief of symptoms, arresting the spread of the rash, minimizing disease pathology and providing a superior quality of life. As a topical cream with no evident adverse effects, NV-HHV-101 should enable strong patient compliance as well.”
The progression of NV-HHV-101 through IND-enabling safety/toxicology studies and the subsequent effort to move its HSV-1 and HSV-2 treatments into the development pipeline are part of the company’s overall strategic goal of proving out its technology platform and bringing antiviral treatments to market.
“We are a technology platform-based drug development company; as our first drug proves through the regulatory process, it will prove that our postulates, and mechanisms, are capable of creating highly effective, valuable drugs against viruses,” says Diwan. “It will be a strong validation with human proof of principle. We have already demonstrated proof of principle in animal models against several viral diseases.”
“The nanoviricide technology has built-in capabilities that allow (i) attacking virus particles outside cells, (ii) attacking virus replication in only virally infected cells, sparing normal, uninfected cells, as well as (iii) eliminating latent viruses from harboring cells,” he explains. “We are currently working on only the part (i) capabilities, which limit viral reinfection, thereby reducing pathology. Our next goal is to additionally harness the part (ii) capabilities, thereby providing a complete cure for viruses that do not have a latency phase. Once these second-generation nanoviricide drugs are developed, we plan on engaging into the third level of capabilities—that of eliminating latent viruses from the body, thereby curing as yet incurable viral diseases including herpesviruses … as well as HIV/AIDS and a number of other viruses.”