Dr Anthony Fauci has recently indicated that getting early-stage treatments for COVID-19 that prevent vulnerable people going on to be hospitalised is a key goal. While he mentioned monoclonal antibody products in development, he was quite vague other than to say that there will be more news on this front soon. I’ve been thinking for some time that while multiple billions of dollars are being invested in vaccine developments, many of which involve unproven mRNA- and DNA-based technologies, it is risky to assume that any COVID-19 vaccine will be available soon. At the moment other than treatments for late-stage critical cytokine storms, there is little news on the treatment horizon either, especially for early-stage disease. Here I report on some indications as to where this might be going and what could be interesting for investors with regard to this relatively neglected space. Small Australian biotech company Starpharma (OTCQX:SPHRY) (OTCQX:SPHRF) may have a solution with SPL7013. In the meantime, social distancing, masks, lots of testing, contact tracing and quarantine are the main weapons to fight the COVID pandemic. The COVID-19 pandemic
I’ve been reflecting on the COVID-19 pandemic as the world economy grinds to a halt. A few years ago my son decided to write a novel/film script about a pandemic and I got involved in trying to develop a story that wasn’t relentlessly obvious. I did a lot of research and came up with some ideas that have some plausibility based on real biomedical information, that kept the reader guessing. I started with thinking about Laitai, sudden unexplained deaths in their sleep of Thai young men. COVID-19 provoked my son, Rufus Williams, to publish his story “The I.F. Zones” and it is just out on Amazon. How can Amazon sell a Kindle version for the price of a cup of coffee?
The above was my son and I being clever about a non-obvious explanation for the cause of a pandemic. COVID-19 is something else. It is obvious, It is relentless and it proves that viruses are designed to find ways to survive even when we prefer not to know about them. There are basically three areas where society can get the better of SARS-CoV-2. Firstly, we can cut off its ability to replicate by denying it a means to propagate. Viruses can only replicate by hitching a ride on the replication machinery of a host cell. So if you cut off the infection sequence, the virus dies out on its last victim. This requires a lot of community involvement and it means that the economy gets destroyed while choking off the virus is happening. Some countries have been relatively successful with this approach (notably New Zealand, a number of Asian countries including China). Others have not been able to get buy-in from citizens and there has been a reluctance to close the economy. This has led to a very large death toll without much benefit as the economy shuts down anyway. Secondly, an effective vaccine would stop the virus in its tracks. Anyone who follows the news will understand that there have been tens of billions of dollars invested in this approach. At this stage it is too early to know if any of the hundreds of vaccine programs will be successful, and if any does become successful, the timing of a successful vaccine is still anyone’s guess. Thirdly, is the possibility of treatments. So far there has been some success with end-stage disease where some mortality has been averted. The treatment area seems to have been less resourced and there seems to be less progress. However, there are some signs of change. Here I show that the pickings are quite meagre. Starpharma SPL7013 antiviral dendrimer
Readers who follow me will be aware that Starpharma is my favourite neglected biotech stock. It is important to note that I’ve been an investor in Starpharma for a very long time and I’ve written a number of articles to explain why I think it will end up being one of those investments that overdeliver even though they require patience.
Given the madness of the COVID-19 vaccine programs, where there is literally an open cheque book and the rules for drug/vaccine development have been comprehensively ignored, it seems quite quaint to report on an early-stage treatment for COVID-19 that is following the rules and seems to have been largely overlooked by the noisy biotech industry. But this is the case for SPL7013. I wrote in May about Starpharma’s SPL7013 and indicated that it might become useful as an early-stage treatment.
SPL7013 is the active ingredient of VivaGel BV, a treatment for bacterial vaginosis that is approved in 39 countries and is becoming a successful product as it is rolled out in these markets. The outlier is the US, where Starpharma has a marketing agreement with ITF Pharma but FDA approval is held up by the FDA for reasons that are unclear. Ironically, it seems that part of the delay in the VivaGel BV FDA application might be preoccupation by the FDA with COVID-related products.
Starpharma recently released its quarterly cash flow and activities report for the quarter ending June 30. It is a busy read, but here I’ll focus on Starpharma’s recent rapid progress in use of SPL7013 as an early-stage prevention/treatment for COVID-19. SPL7013 is being marketed around the world as VivaGel BV for treating bacterial vaginosis (it also has antiviral activity), which is a poorly treated disease affecting a significant percentage of women worldwide. SPL7013 is also the active antiviral ingredient in a range of VivaGel condoms which are approved for sale in Europe, Canada, China, Japan and Australia. Starpharma has shown that SPL7013 has activity in the test tube against SARS-CoV-2 which causes COVID-19, and it has patented use for preventing and early-stage treatment of COVID-19. While the story is evolving, the Quarterly report gives some more detail concerning what Starpharma has planned for a COVID-19 early-stage treatment with SPL7013.
SPL7013 acts by binding to SARS-CoV-2 surface proteins, hence interfering in the critical step for infection of human cells. SPL7013 was optimised for delivery to vaginal mucosal surfaces. The nasal cavity is another mucosal surface and the company is confident that the formulated version of SPL7013 will act similarly in the nasal cavity to the way it acts in the vagina. A liquid formulation binds to the mucosal surface and when the SPL7013 comes into contact with SARS-CoV-2, the virus binds to it and becomes inactivated, thus preventing infection of cells. Note that SPL7013 prevents cell entry, which is the first stage of viral infection.
A nasal spray containing SPL7013 (which has been patented) will be useful for additional protection from infection for front line workers (e.g., medical workers contacting potential COVID patients, aged care workers, police, etc.) as well as family members and carers of COVID patients. While Starpharma is developing SPL7013 in a nasal formulation, it most likely can be adapted for both inhalation (including using a nebuliser) and also for eye drops. A formulation for eye drops provides an effective treatment of adenoviral conjunctivitis (SARS-C0V-2 not yet tested?). The nasal formulation is especially effective for upper respiratory tract applications (i.e., initial phase of an infection), while a nebuliser formulation (smaller particles) would be more geared to lower respiratory tract (i.e., later stage) infection.
During the last quarter, Starpharma has been in discussion with regulators (most likely in Europe) concerning configuration of SPL7013 as a COVID-19 nasal spray. It will require minimal re-development, as there is a deep body of technical data for SPL7013 and existing regulatory approvals. Hence Starpharma is anticipating accelerated development and accelerated launch of the product to protect from and treat early-stage COVID. Europe is a big market, with VivaGel BV currently becoming marketed throughout the UK, Germany, Central and Eastern Europe. No doubt there is likely to be considerable interest in the COVID product as Europe’s experience of the COVID pandemic has been traumatic and there are recent new outbreaks (e.g., yesterday 5,760 new cases and 26 deaths in Spain, and 1,039 new cases and 2 deaths in France).
Starpharma reports specialist clinical feedback to be strongly supportive of the early-stage prevention and treatment in the COVID program. It is seen to fill an important gap in reducing transmission and complementing vaccine-based programs.
Note that SPL7013 is a general antiviral drug that is effective against a number of viruses and hence it might prove to be suitable for early-stage protection against other viruses that might be involved in future pandemics. This might provide interesting market opportunities for stockpiled antivirals.
There is more to the Starpharma story concerning its drug delivery platform (DEP) that I’ll reserve for another update. Targeting remdesivir to the lungs through nebulised and inhaled delivery?
Remdesivir is a nucleoside RNA polymerase inhibitor. It interferes with viral replication and its mode of action occurs after the virus has infected cells. So this impacts on the COVID disease process at a later stage than Starpharma’s SPL7013.
Remdesivir is one of two treatments for COVID-19 that are accepted as likely to be effective in treating late-stage COVID-19 (the other is the corticosteroid Dexamethasone, which is only suitable for lowering late-stage mortality). Remdesivir is delivered as an injectable drug which is suggested to result in earlier release from hospital in critically ill patients. It is not yet clear if remdesivir lowers mortality.
Gilead (NASDAQ:GILD) is developing a nebulised inhaled version of remdesivir to be used outside of a hospital setting with the goal of preventing hospitalisation. A phase 1a trial involving 60 healthy adult volunteers in the US was initiated in early July. At this stage it is unclear whether this treatment option will require medical supervision, or whether patients will be able to self-administer at home should this route of delivery prove to be effective.
Clearly, the goal is to extend the market opportunity for remdesivir beyond people suffering from severe COVID symptoms. Favipiravir
It has been suggested that antiviral favipiravir might be suitable for treating early-stage COVID-19, but later studies suggest that favipiravir is ineffective for treatment of COVID-19. BioCryst's (BCRX) Galidesivir as a nasal spray?
Galidesivir, like remdesivir, is a nucleoside RNA polymerase inhibitor. It has broad spectrum action against more than 20 RNA viruses (including coronaviruses). The status of its development is less clear than remdesivir's but it is likely to be useful for injection of patients with severe COVID disease.
Whether or not galidesivir may be suitable for oral/inhaled delivery for early-stage treatment is unclear. Other treatments
The above is a very skinny list of potential treatments for COVID-19. The NIH (National Institutes of Health) is seeking to expand the list of treatment candidates by preparing to launch a “flurry” of large clinical trials in search of additional treatments. The kinds of drugs being contemplated remain vague (but probably not for long). There are clearly a lot of monoclonal antibody treatments that might impact immune system dysfunction in late-stage COVID patients and heparin-like compounds that might help counteract microclots that seem to be a common feature of severe COVID infections. There are inconclusive results from use of convalescent plasma to treat COVID patients. Conclusion
When I started writing this story I expected that I would find a number of treatment candidates that have become clear possibilities for early-stage treatment. I have been very surprised to find that at least at this stage this is not the case. Perhaps Anthony Fauci is correct in indicating that there is going to be a lot of progress with trials that are currently underway. On the other hand, had there been anything to report I would have expected to have seen it in the New York Times by now. It brings a smile that apart from possibly making remdesivir useful for early-stage treatments, the only really concrete candidate is SPL7013 that comes from my favourite Aussie small biotech company. Starpharma’s approach seems quaint in today’s hyped-up world. The company is diligently doing all of the things that one has traditionally done to get a new drug to market. Should it succeed with getting approval for early-stage COVID prophylaxis and treatment in Europe sometime soon, I’m sure I’ll end up a very happy investor.
I am not a financial advisor but I do follow biotech closely and have made some personal calls about micro-companies (including Starpharma) that seem to me to have good prospects. I’ve said in my earlier Starpharma articles that this company might be one for discussion with your financial advisor as a candidate for the high risk end of your portfolio. Disclosure: I am/we are long SPHRY. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.
SPL Price at posting:
$1.08 Sentiment: Buy Disclosure: Held
