COVID-19 Vaccine Stocks To Watch (June 2021)
Summary
Many Smid-Cap COVID vaccine developers are still actively pursuing COVID vaccines
Catalyst readouts from these companies are still driving their stock prices
OCGN was a June 2021 Big-Mover stock to watch that disappointed when it announced that the FDA guided it to submit a full BLA instead applying for Emergency Use Authorization EUA
Smid-Cap COVID vaccine companies are still interesting to investors because they are focused on overcoming supply chain storage, administration, and variant efficacy issues
ALT is a stock to watch with its upcoming clinical trial read outs this month for its COVID vaccine and therapeutic candidate
ALT's COVID vaccine is potentially differentiated by its nasal administration route, but thus far we only have preclinical data
As we discussed in our last COVID-19 vaccine company update for investors in late April, the opportunity has shifted to ex-U.S., boosters and coronavirus variants. Table 1 below is a list of small and mid-cap COVID-19 vaccine companies that are listed on a U.S. stock exchange and have a clinical stage Covid vaccine, along with some that are still in preclinicals. This is a comprehensive list of U.S. stock market listed small and mid-cap biotech Covid vaccine companies in clinical development as far as we have been able to determine. If you are aware of others, please comment below. We included NVAX on this table even though it has a market cap over $12 billion since it is still in the clinical development stage and since we had it in our database from when it was under $5B market cap. DVAX and OCGN are partners for vaccines that are already on the market in certain countries.
DVAX is quite interesting because its CpG 1018 adjuvant technology is used in a number of Covid vaccine candidates. There was a deal between DVAX and Sinovac, a leading Chinese vaccine company, but it does not appear to be in CoronaVac, Sinovac’s COVID vaccine, which is approved in a number of countries including China (See Sinovac’s CoronaVac product page). It is unclear whether the Dynavax and Sinovac collaboration is still active (Dynavax and Sinovac Announce Collaboration to Develop a Coronavirus (COVID-19) Vaccine). However, Dynavax provides this key adjuvant for a number of vaccine candidates, see INRLF's VLA2001 for example, and has received $100s millions in U.S. government funding because of it. For investors, DVAX has been a winner in 2021, as the stock has doubled in value this year.
One of our June Covid vaccine Big-Mover stocks to watch was OCGN (See our June Big Mover Blog post) or June Big Mover Forum post for subscribers). OCGN holds U.S. rights to COVAXIN (Figure 1), the vaccine developed by Bharat Biotech and the Indian Council of Medical Research (ICMR) - National Institute of Virology (NIV). COVAXIN™ is currently being administered under emergency use authorizations in 13 countries, and applications for emergency use authorization are pending in more than 60 additional countries. It is noteworthy that OCGN has a daily volume that is almost 5x the next highest Covid vaccine company, IBIO. In an unusual step, earlier this year, its CEO communicated progress toward U.S. regulatory filing on Linked-In (Ocugen extends gains as CEO hints on EUA submission for COVID-19 vaccine). OCGN’s share price fell 28% earlier this month when they announced that the FDA guided them to run another trial and file a full BLA, rather than seek Emergency Use Authorization (Ocugen to pursue a BLA path in the US for its COVID-19 vaccine candidate). However, despite the 28% drop, OCGN has given investors over a 250% return in 2021 thus far.
Table 1. Covid Vaccine Candidates for Biotech Companies*
*Biotech companies with valuations between $100M and $5B
SUBSCRIBERS VERSION BELOW THIS POINT
In the current commercial landscape, mRNA technology seems to be a stand-out given Pfizer/BioNtech and Moderna's success thus far. In speed to market, this technology is the clear winner. It is noteworthy, possibly due to intellectual property concerns, that we don't find any mRNA smid-cap Covid vaccine companies. However, there are many different technologies in development by smid-cap Covid vaccine companies that could be important for global herd immunity and/or future boosters to protect against coronavirus variants (See Table 2). In fact, most or all of the smid-cap vaccine companies are attempting to overcome the ultra-cold storage issues of mRNA vaccines (Table 2). VXRT appears unique amongst these investible smid-cap COVID vaccine players with an oral vaccine.
Table 2 . COVID vaccine candidate details
With respect to interesting smid-cap COVID vaccine companies, a Big-Mover stock to watch this month is Altimmune (ALT) with its COVID vaccine, AdCOVID. AdCOVID is a nasally administered vaccine that is room-temperature stable for several months (See Altimmune AdCovid page). Altimmune expects to report data on its COVID-19 vaccine, AdCOVID, and its COVID-19 therapeutic, T-COVID, this month. AdCOVID and T-COVID are particularly interesting because they are administered intranasally. This is particularly interesting because it has been reported that the highest expression of the receptor targeted by coronavirus, the ACE2 receptor, is in the nose (Hou YJ, Cell 182, 429–446, 23 July 2020), and intramuscular COVID-19 vaccines are not believed to elicit an immune response in mucosa (Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice).
AdCOVID is an adenovirus that targets the spike protein RBD (receptor-binding domain) and is currently in a Phase 1 trial which was initiated in February 2021. Preclinical data in mice has shown that AdCovid can induce multiple arms of the immune system including neutralizing antibodies, mucosal IgA, and T cell responses with improved activity using the receptor binding domain (RBD) construct vs. the full length or S1 subdomain of the spike protein (Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice). Altimmune is betting that a single-dose simple nasal spray will elicit not only neutralizing antibodies and anti-coronavirus T cells, but nasal mucosal immunity, which is a common site of viral entry. Preclinical data reported in the first quarter of 2021 showed there was a 29-fold induction of mucosal IgA in the respiratory tract by Day 21 (Figure 1) as well as an increase in T cells in the lungs and spleen (Figure 2) (Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice).
FIG. 1 Antibody responses in preclinical trials in mice (SOURCE (slide 14))
FIG. 2 T cell responses in preclinical trials in mice (SOURCE (slide 16))
The ongoing Phase 1 trial includes healthy volunteers in 6 cohorts with immunogenicity endpoints including spike IgG antibody levels, virus neutralizing antibody titers against SARS-CoV-2 virus, T cell responses, and antibody responses. The safety endpoint includes adverse events and reactogenicity. The hope is that AdCOVID can be used as a booster following initial vaccination or to address concerning variants as none of the current vaccines elicit mucosal immunity. ALT reduced the number of adult subjects in its Phase 1 trial to 80 participants to be comparable to the Phase 1 studies of authorized vaccines.
Altimmune has also started preclinical evaluation of AdCOVID to target E484K variants, and a Phase 2 trial in this study is expected in the fourth quarter of 2021. Initial preclinical data from this trial show the neutralizing titer against the B.1.351 variant virus was only 4.4-fold lower than the neutralizing titer against an original or ancestral Wuhan-like isolate seven weeks after dose and was only 1.8-fold lower seven weeks after a booster dose was given (Altimmune Demonstrates Strong Neutralization Of South African Variant In Preclinical Study Of Intranasal AdCOVID™.
On the negative side, ALT is far behind competitors with respect to its COVID vaccine, without any human clinical data currently. Furthermore, as an adenovirus vector-based vaccine, it is more likely that this vaccine would induce rare thrombotic events (See our prior article on the rare thrombotic events). Just how rare given only the RBD domain is expressed and given the nasal delivery, will not be known until this vaccine is administered in 100,000s or millions of humans.
T-COVID is Altimmune's intranasal therapeutic currently in a Phase 1/2 clinical trial. This asset could be self-administered as a therapeutic for early COVID-19 to reduce lung inflammation and the inflammatory cytokine response. Preclinical models showed this therapeutic provided protection within days of administration and there was near immediate protection from other respiratory pathogens such as influenza (Figure 3). The Phase 1/2 trial includes 96 patients in three cohorts of increasing age and risk for complications of COVID-19 who had fever, cough, or shortness of breath with onset of symptoms (confirmed to be COVID-19 within 72 hours). The primary efficacy endpoint for this trial is the proportion of patients with clinical worsening (a 4% decrease in SpO2) or hospitalization. Additional secondary endpoints include average decrease in SpO2, average increase in resting pulse rate and the proportion of patients requiring oxygen and mechanical ventilation. Data from the Phase 1 portion is expected in the second quarter of 2021.
FIG 3. Survival curves after T-COVID administration in preclinical studies
With respect to the upcoming phase 1 COVID readouts for ALT, from our experience, the COVID vaccine candidate is more likely to show positive results than the therapeutic candidate. This is based on the fact that other COVID vaccine candidates thus far have appeared to perform at least pretty well in human Phase 1 trials when they have shown good efficacy in preclinical testing. How well the data will look compared to other vaccine candidates will likely be judged in large part based on neutralizing antibody activity. It is interesting to note that at the highest dose, the RBD vaccine used in their Phase 1 trial, induced neutralizing antibodies in 10 of 10 and 8 of 10 mice (Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice at page 8 (and See Figure 4)). However, we don’t know how well mice data will apply to human studies, given intranasal delivery and at the selected doses.
FIG. 4 Neutralizing Antibody Activity in preclinical trials in mice (SOURCE (slide 15))
Although it's difficult to predict how well AdCOVID or T-COVID will look in these first in-human clinical trials, and ALT is far behind in the race for COVID vaccines and therapeutics, these are important clinical assets that could significantly impact our future response to COVID. Based on the importance of these assets to ALT and the important readouts this month, as well as stock options activity currently, ALT stock price is likely to move significantly if the data is strongly positive or negative for either of these trials. Of course, it is helpful that there are 2 upcoming shots on goal this month for ALT. Furthermore, since ALT has a number of assets in its pipeline, poor results in both readouts will likely negatively impact the stock more than 25%, they shouldn’t completely eliminate ALT’s value (See https://www.bpiq.com/companies/ALT).
Feel free to comment with your thoughts on ALT and these upcoming COVID readouts. Want to find the next big readouts for COVID vaccine companies? Just search our catalyst calendar for COVID vaccines.
By: Faith Smalley (M.Sci) and Manny Vacchiano (JD, PhD) at AmpBioResearch (BPIQ.com)
This article is NOT investment, tax, or legal advice. Please use this as a starting point for your detailed diligence and consult professional advisers before making investment decisions.
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