RiVax® Demonstrates Durable Immunity in Mouse Model
On November 4, 2021, Soligenix, Inc. (NASDAQ:SNGX) announced the publication of preclinical studies for RiVax®, the company’s heat stable ricin toxin vaccine) that showed durable protection for at least 12 months following immunization (Novak et al., 2021). Ricin toxin (RT) is one of the most lethal toxins known. It is a protein produced by the castor bean plant this is composed of two subunits, and once it enters a cell it incapacitates protein production through ribosome inhibition, which leads to cell death. RT can be lethal whether it is ingested orally or inhaled, although it is more potent through the inhalation route.
For this study, a prime-boost strategy was employed and the durability of protective immunity and RT-specific antibody responses were evaluated. Twelve groups of mice were immunized subcutaneously with RiVax (3 μg; n=12 per group) on days 0 and 21. The mice were then challenged with a dose of RT that is ten times 50% of the lethal dose (LD50) on days 35, 65, 95, 125, 245, and 365. Two other groups of mice were immunized with a low dose of RT (1 μg) on days 0 and 21 and then challenged with RT on days 35 and 365.
Results showed that the group of mice that received 3 μg of RiVax and were challenged with RT on day 35 had a 92% (11/12) survival rate, with all the mice that were challenged on successive time points surviving. The survival rate was lower for mice that received the low dose of RiVax (1 μg); mice challenged with RT on day 35 had a 75% (9/12) survival rate while mice challenged on day 365 had a 92% survival rate (11/12).
The durability of the antibody response is shown in the following figure. By day 30, there was an approximately 5-fold significant difference in antibody titers between mice that received 1 μg and 3 μg. However, by day 60 the antibody titers were similar. Thus, while the higher dose of RiVax leads to a higher antibody titer sooner, antibody levels remained steady through 12 months post-vaccination.
To investigate the efficacy of a single dose of RiVax (3 μg), twelve mice were immunized with RiVax on day 0 and then challenged with RT on days 35, 65, or 95. As the following graph shows, the single vaccinated mice did not fare as well as mice that received two doses of RiVax. The survival rate for mice challenged on days 35 and 65 was just 17% (2/12) and for those challenged on day 95 it was 33% (4/12), compared to 100% for mice who received two doses of RiVax. Antibody analysis showed that a single dose of RiVax elicited a significantly lower antibody titer than two doses of RiVax. Taken together, these results indicate that a single dose of RiVax is unlikely to be efficacious.
Soligenix will pursue approval for RiVax under the FDA’s “Animal Rule”, which relies upon studies conducted in animals to gauge the effectiveness of a product candidate if testing of that product in humans would be unethical (as in the case of ricin exposure). Upon approval, RiVax would be eligible for a priority review voucher (PRV), which are fully transferrable and recently multiple PRVs have sold for approximately $100 million each.
SGX302 to be Developed as Psoriasis Treatment
In September 2021, Soligenix announced that it will be expanding the potential market for synthetic hypericin under the research name SGX302 into psoriasis. Psoriasis is a common, chronic, noncontagious, multisystem inflammatory condition that most commonly presents on the skin of the elbows, knees, scalp, back, and thighs. There are multiple types of psoriasis, with plaque psoriasis, being the most common and affecting 80-90% of all individuals with psoriasis. Plaque psoriasis involves the hyperproliferation of epidermal keratinocytes that results in red or white, scaly, and typically itchy skin lesions. In addition, approximately 20% of psoriasis patients suffer from psoriatic arthritis, an inflammatory joint disease associated with psoriasis (Zacharlae, 2003). There is no known cure for the disease, thus depending upon the severity of the condition and how responsive it is to treatment, some patients are on therapy for life.
While psoriasis itself is not life-threatening, there are several conditions that are associated with the disease, including cardiovascular disease (Shlyankevich et al., 2014) and hypertension (Armstrong et al., 2013). In addition, patients with psoriasis have an increased risk for a number of non-skin cancers, including cancer of the lung, upper gastrointestinal tract, urinary tract, liver, and pancreas (Richard et al., 2013).
The severity of psoriasis is dependent on how much of a person’s body surface area (BSA) is affected by the condition. Mild psoriasis typically covers <3%, moderate covers between 3-10%, and severe covers more than 10% (National Psoriasis Foundation). However, the severity of the disease also takes into account how it affects a patient’s daily life, with even small psoriatic lesions on the palms or soles of the feet capable of having a severely negative impact on an individual’s quality of life.
Soligenix previously tested synthetic hypericin in a small Phase 1/2 trial involving 13 patients with psoriasis (Rook et al., 2010). Results showed that of the 11 evaluable patients, six responded to treatment with hypericin. There were no deaths or serious adverse events and the only reported adverse events were mild to moderate and included itching, burning, erythema, and pruritis at that application site.
The company is currently evaluating different topical formulations of synthetic hypericin while at the same time working with psoriasis experts to finalize a clinical trial protocol. We anticipate a Phase 2a study initiating in the second half of 2022. We estimate that the company has sufficient capital to conduct the trial without the need to raise additional capital.
On November 12, 2021, Soligenix announced financial results for the third quarter of 2021. The company reported revenues of $0.2 million for the third quarter of 2021, compared to $0.6 million for the third quarter of 2020. The decrease in revenue is primarily the result of the completion of the RiVax contract. R&D expenses for the third quarter of 2021 were $2.5 million, compared to $1.3 million for the third quarter of 2020. The increase was primarily due to the continued development of HyBryte. G&A expenses for the third quarter of 2021 were $0.9 million compared to $0.8 million for the third quarter of 2020. The increase was primarily due to an increase in legal and consulting services and the arbitration against Emergent BioSolutions.
Soligenix exited the third quarter of 2021 with approximately $28.9 million in cash and cash equivalents. As of November 10, 2021, Soligenix had approximately 42.9 million shares outstanding, and when factoring in stock options, warrants, and the potential convertible debt the fully diluted share count is approximately 53.0 million.
The company continues to generate positive data for its Public Health Solutions business. The data discussed above for RiVax is very encouraging and adds to the previous data showing robust immune protection in another animal model. We look forward to additional updates on RiVax as the company continues its development. Soligenix has a strong balance sheet that will carry it through important upcoming milestones, including filing the NDA for HyBryte in the second half of 2022. With no changes to our model our valuation remains at $6.00 per share.
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