Last week, Soligenix (NasdaqCM: SNGX) offered some useful and compelling insight into its CiVax program to develop a broadly distributed COVID-19 vaccine. The news helps put the program back into the competitive spotlight as one of the most promising and potentially useful vaccines in current development. Although the large caps tend to earn the headlines, some critical distinctions in the CiVax platform deserve far more attention than it is getting.
Soligenix is not new to the biopharmaceutical sector. They are a late-stage development company focused on developing and commercializing products to treat rare diseases where there is currently an unmet medical need. The company has two unique focus areas: a specialized biotherapeutics business segment dedicated to oncology and inflammation, and a separate public health solutions business segment funded entirely by the government focused on vaccines and therapeutics for civilian and military applications.
The rare disease pipeline benefits from its programs being orphan and/or fast-track designated. More important, especially in the expense category, is that they are funded in part or entirely by the government. That funding has allowed Soligenix to not only move excellent technology forward but allows them to build out a more robust pipeline than you would typically see for a company its size with multiple shots on goal to mitigate risk. This funding also allows the company to manage cash-burn very effectively.
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Late-Stage Trials In Progress
Currently, the company’s specialized biotherapeutics business has two Phase 3 clinical programs in progress. The first is SGX301, its topical synthetic hypericin, in cutaneous Tcell lymphoma. For this Phase 3 program, the company announced top-line positive results in its primary endpoint earlier this year and expects to release additional follow-on data in the fourth quarter of 2020.
The second Phase 3 program is SGX942, using a new chemical entity dusquetide, in oral mucositis in head and neck cancer. This Phase 3 study has completed enrollment following a positive interim analysis and expects to deliver final top-line primary endpoint results in the fourth quarter of this year. The market for oral mucositis can be substantial, and the company has noted that the potential for business development activity can follow the same course.
Both programs can offer tremendous upside potential based on continued positive results. And, being with each trial working to confirm already positive results, the chances are that the results will not disappoint.
However, it’s the Public Health Solutions business that is starting to earn its share of attention.
CiVax Vaccine Program For COVID-19
Transitioning to the Public Health Solutions business segment, the company is again pursuing non-dilutive government funding to advance the program. In a recent conference, Soligenix noted that they are in various phases of seeking funding that they believe will be in its future. They also say that they will not plan to use their own funds to advance the program.
For those following other COVID-19 programs, they are extensive and costly programs. Thus, the company will need additional non-dilutive funding to advance the trial. Currently, the company has roughly $11 million in cash as of its last 10-Q. With the other financial instruments at its disposal, like non-dilutive government funding, the company believes their cash allows them to reasonably get to those near-term catalysts from the top-line Phase 3 results in oral mucositis.
A quick disease background on COVID-19 is that it is a respiratory illness that is caused by SARS-coronavirus-2. This is a virus similar to the original SARS coronavirus that caused the limited outbreak in 2003. As a respiratory virus, droplet transmission via the aerosol route is believed to be the primary mode of transmission, particularly in enclosed spaces. These viruses use their spike protein, which is a trimeric glycoprotein that sits on the viral surface, for viral entry through the human ACE2 receptor, which is a receptor that is very prevalent in cells of the respiratory tract. The main disease driver is that, basically, a dysregulated inflammatory response, particularly a more undefined innate immune response, drives, then, the pathology seen.
Mainly, inflammation can be caused by adaptive immune cells later on or from the death of certain types of immune cells. What is really important is that the inflammatory response dramatically enhances the damage to the lung tissue and other areas, causing acute respiratory distress, which is a primary driver of mortality. Treatment options, as it is a relatively young disease, the focus is mainly on severe disease, so therefore, remdesivir, which has been approved for emergency use, can decrease the length of hospital stay but has not yet been shown to increase survival. And then another treatment is dexamethasone, which appears to reduce mortality. Understandably, there is a significant focus on these acutely ill patients; unfortunately, that means that mild or moderate cases of COVID-19 disease — these are patients that are hospitalized — they basically just receive supportive care; thus, oxygen and standard treatment, and there is no treatment so far for patients that don’t require hospitalization.
The vaccine development efforts for this disease are unprecedented and use various vaccine platforms to combat the virus. Soligenix’s is unique. Clearly, the main driver for vaccine platforms is to target all types of patient populations, and that’s mainly driven by the safety profile of the individual platform. Also, logistical requirements are different for different platforms. Mostly, storage and distribution are vastly different and could range from ambient temperature to ultra-low frozen temperature. Dosage requirement is something else that may change between vaccines; most of the platforms right now seem to require two doses. And then there are differences in the manufacturing requirements, mainly in terms of the facilities and in terms of the raw product needed to manufacture the product.
Another thing that remains unknown is the durability of the immune responses. This is also different for different platforms, and, in truth, professionals don’t know yet, based on the virus’s epidemic characteristics, whether yearly or seasonal vaccinations may be required. Fortunately, what is known, is that from some candidates that have advanced further in the clinical process that immune responses can be achieved in humans.
Vaccines In Development
Currently, there are more than 200 candidates in development. Of those, about 30 are in clinical trials, and six presently in the late-stage Phase 3 human clinical trials. Soligenix is focused on an antiviral vaccine platform that uses a protein and directly delivers the protein to the person being vaccinated to generate an immune response. More specifically, the goal is to create an antibody and a cell-mediated immune response to the protein marker of the virus you’re trying to vaccinate against.
Through its collaboration with the University of Hawaii, the program has been very productive. As part of that program, Soligenix licensed the CoVaccine adjuvant because of it’s demonstrated ability to stimulate antibody and cell-mediated immunity. Importantly, though, Soligenix adds another level of value through a thermostabilization platform that enables co-lyophilized formulation. Any product produced would be thermostabilized and, therefore, can be shipped ambiently, thus eliminating concerns about the need for refrigerators, freezers or ultra-low freezers since the products are planned to be stable to 100 degrees F.
Ideally, the vaccine candidate is produced as a single vial, with some white powder in the bottom of it. The only thing that needs to be done to vaccinate would be to add sterile water for injection immediately before use. In its RiVax program, the company showed an ability to drive that potency to 12 months at 40 degrees Celsius, so thermostabilization can be a crucial aspect of the overall program.
Again, the push is to develop an antiviral protein vaccine on a protein-based platform. That can be advantageous because the protein platform is equally applicable to older populations and the immunocompromised; thus, it allows for the broadest possible application. Protein vaccines have been used for many years, and their safety and their characteristics are very well understood. The program is boosted by an adjuvant that allows the company to get maximum potency out of a vaccine, having licensed a CoVaccine from Boston Scientific (BSX).
This particular adjuvant has been tested previously in Phase 1 and Phase 2 clinical studies, identifying its maximum tolerated dose. Also noted is that it’s safe to use in humans and can be consistently produced at scale.
Benefits Of CiVax
So what are the benefits, then, of CiVax? In simplest terms, prototype work has demonstrated that the vaccine produces that critical Th1 response. That result is not only in the antibody response but also in the cell-mediated response. Also, as with its original prototype vaccine, the antibody response was produced very quickly, within 14 days of the first vaccination.
That speed of reaction means a patient gets partial protection relatively quickly after vaccination, which during an outbreak scenario can be really important. The protein platform also gets around development risks associated with RNA vaccines. Therefore, by using the protein platform that is well understood, Soligenix may have made sufficient breakthroughs in terms of thermostabilization and using the appropriate adjuvant to push both potency and give them some real advantages in terms of logistical constraints in distribution. Again, they will also be able to manufacture with a stably transformed cell line, has useful proof-of-concept data, and have shown that they can use protein-specific chromatography to get a very clean product at the end.
Clearly, one of the emerging issues is the storage and shipment issue, especially as some of the candidates require not just freezing but freezing at minus 70 degrees Celsius. And it’s important to note that when you don’t make your storage conditions, additional downstream costs arise. First is the one that you know didn’t meet their storage conditions and therefore have effectively been wasted and have to be thrown out because they went outside their storage parameters. But the second cost is the ones where it is unknown whether the vaccines went outside their storage parameters, and now presented with the dilemma of potentially giving a vaccine to people that are not going to be as potent as it should be.
Another vital advantage of CiVax is its makeup. It’s one thing to have a supply chain for a single vial; it’s another thing to have to ship two components, and both have their own storage requirements. Thermostability, in that respect, may be the preferred option.
Consider this, as well. This pandemic is a humanitarian crisis with a total addressable market for the COVID-19 vaccines estimated at about $23 billion. To put that into context, the current global vaccine market in its entirety is about $40 billion, so clearly, a massive opportunity exists for the COVID-19 vaccines.
Soligenix believes they are on the right track by developing what they believe to be the gold standard vaccine platform. In fact, many of the vaccines in development for COVID-19 are using the subunit technology as well, so the company is on-trend, and they think it will bode well for FDA clearance and public acceptance. And finally, when it comes to seasonal use, they believe that CiVax could be used as a booster on an annual or semiannual basis and can be used in conjunction with or in addition to whatever vaccine technology was employed for the first dose.
Setting Up For Catalysts
Combined, Soligenix has multiple shots on goal to create significant transformative events at the company. Their collaborations with biotech, academia, and government agencies position the company to do well on the development front.
And with Soligenix hoping to have nonhuman primate data by the end of the year, which is not even a prerequisite for starting a Phase 1 study, that value can accrue soon. Moreover, when comparing CiVax to RNA vaccines like those that are under development by Moderna or Pfizer, which generally require two does to get a robust immune response, CiVax may prove to be a better and more temperature stable option.
They have already shown from the early preclinical data that the immunogenic response is rapid. This means that CiVax can not only be used as a primary vaccine but can also have a significant value as a booster vaccine that could be used six to 12 months after the primary vaccine.
In each of the company’s studies, though, they are showing a common denominator. Each program is unique, targets extreme and unmet medical conditions, and is shown to be effective through its critical stages of trials. Those results deliver confidence, and the CiVax program may be the next to earn accolades.
Please visit https://get.ceo3in60.com/soligenix-bio/ for more information about Soligenix
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