BioNTech: Covid Market Expansion Plus CAR-T Therapy Improvements (NASDAQ:BNTX)

BioNTech SE (NASDAQ:BNTX) is a great long-term biotech to look into. The reason why I believe it is a great company to hold for a long period of time is because it currently is and will continue to produce revenue of Comirnaty for Covid-19 with its partner Pfizer (PFE). Not only that, but what is also a good move for the future, would be the potential to expand upon this opportunity.

Such expansion opportunities will come with several pathways. The first pathway would be to enhance the efficacy of the Covid-19 vaccine with an enhanced spike antigen vaccine. This is being done through exploration of such a candidate with a phase 2 study. Another pathway for expansion into this market will be to use a T-cell enhancing SARS-CoV02 vaccine candidate (BNT164b4) in combination with the original/omicron BA.4/BA.5-adpated bivalent Covid-19 vaccine. This was said to have entered the clinic in Q4 of 2022, and data later on could also allow for an expansion opportunity.

Most notably, I would say the best expansion would come in the form of developing a pan-corona virus vaccine. A vaccine as such that could be capable of targeting all future strains. SARS-CoV-2 is nothing that will ever go away and mutations of this virus are likely to continue for the foreseeable period. Lastly, it has a very diverse pipeline, whereby it is going after other indications using its messenger RNA (mRNA) technology. One of these other candidates in the pipeline would be BNT211, which is a CAR-T cell therapy being developed for the treatment of patients with advanced cell tumors.

The reason why I believe this and other candidates have so much potential is due to BioNTech’s ability to combine its different technologies together. For instance, BNT211 is a combination of a CAR-T cell therapy targeting the antigen Claudin-6 (CLDN6) with a CLDN6-encoding CAR-T cell amplifying RNA vaccine (CARVac). Combining its technologies together allows it to target hard-to-treat indications. With the ability to expand itself in the Covid-19 treatment market, plus potential to combine its technologies together, these are the reasons why I believe it is a great long-term play to look into.

Covid-19 Expansion Continues With Additional Efforts

The main thing about BioNTech and its partner Pfizer is that they continue to generate revenues for Comirnaty. Matter of fact, it raised its Covid-19 vaccine revenue guidance to the upper end of the original range: $16.87 billion – $17.92 billion from $13.71 billion – $17.92 billion. The reason why this guidance was raised in such a manner was because of the sale of Omicron-adapted bivalent vaccine boosters, which shipped in September 2022. As I stated above, however, there are many ways where the company can continue to expand its market opportunity with respect to the Covid-19 vaccine market.

The first strategy is to expand on efficacy and the Covid-19 market space would be to advance candidate BNT162b5. How so? Well, BioNTech and Pfizer are testing out this candidate, which has an enhanced spike protein. Such modification was done to see if the vaccine could provide superior protection against Covid-19, compared to the vaccines that it has released thus far. Not only that, but also the possibility to see if the immune response could last for a longer period of time. In essence, not having the need for booster vaccines being given often. The dose that both companies are deploying for BNT162b5 is going to be at the 30 µg dose level. A phase 2 study to evaluate this specific dose had been initiated in July of 2022. There will be a total of 200 U.S. patients enrolled for this study in order to evaluate safety, tolerability and immune response of BNT162b5.

This bivalent vaccine is going to be a two prong approach, meaning that it will target the SARS-CoV-2 ancestral strain (wild-type) and the Omicron variant. One item to point out is that such a vaccine is going to be tested in patients who have already received one booster dose of a U.S. authorized Covid-19 vaccine at least 90 days prior to being entered into this trial.

The second strategy being deployed would be to advance a SARS-Cov-2 vaccine product candidate by the name of BNT164b4 in combination with the Original/Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine. This was said to enter the clinic in Q4 of 2022, and it will be important to see if such a combination can enhance efficacy. What makes this candidate special, besides being deployed as a combination, would be the addition of T-cells. Thus, BNT164b4 is a T-cell enhanced SARS-CoV-2 vaccine candidate.

The third strategy being deployed is to advance multiple vaccine candidates, besides the ones noted above. The goal is to eventually develop a pan-SARS-CoV-2 vaccine candidate. This means, a vaccine candidate possibly being able to provide protection against all strains of the SARS-CoV-2 virus, not just a few strains. With all these long-term strategies being deployed, I believe that BioNTech is capable of continuing to generate shareholder value in the coming years.

Combination Of Two Proprietary Technologies Could Pave The Way For Improved CAR-T Therapies Against Solid Tumors

Besides the ability to use mRNA to be used in vaccines to target infectious diseases, it is also advancing several candidates for oncology. In particular, what’s intriguing is BioNTech’s ability to combine two proprietary platforms in a synergistic manner. This ability lies with the advancement of BNT211, which is a novel chimeric antigen receptor (CAR) T cell therapy. The nature of this CAR-T is to combine it with another one of the company’s proprietary CARVac technology. CARVac, stands for CAR-T cell-amplifying RNA vaccine. The goal of BNT211 is to target CLDN6+ solid tumors. What makes this CAR-T candidate special, is its ability to target Claudin-6 with a high specificity. Specificity, meaning the ability to reach the correct target at a rapid pace, while at the same time only going after said target. In other words, only targeting the tumor cells it needs to and having no negative effect/impact on healthy cells in the body. The CARVac technology will provide in-vivo expansion of CAR-T cells, which could be capable of having improved persistence and efficacy. The main goal of BNT211 is to overcome the problems associated with current CAR-T cell therapies against solid tumors.

The thing is that CAR-T has done pretty well in being able to treat hematological malignancies, but has not done so well against solid tumors. The reason why this is the case has to do with several reasons, and they are as follows. The first reason is the lack of significant recognition of the CAR-T in the microtumor environment. That is, the ability to not recognize its target in an expeditious manner.

The second reason is the trafficking effect of said CAR-T therapy. Meaning, the ability to reach its intended target through the cell tumor mass. The final reason is largely attributed to poor tumor survival. That is, T-cell activity is weakened in the microtumor environment. The hope for BioNTech is that by adding its CARVac technology it can overcome these limitations. My take is that expansion of T-cells, plus their ability to persist for a longer period of time, might be important factors for achieving improvements for CAR-Ts.

There are other advancements being done, such as armored CAR-Ts, but there again may lie an issue, with Cytokine Release Syndrome (CRS) being an issue. The hope with BNT211 lies not only to have two technologies by BioNTech to be synergistically combined, but the ability to go after Claudin 6 or CLDN6 specifically. That’s because CLDN6 is an oncofetal cell surface antigen only found in multiple types of cancers, however, is not found in healthy cells. As such, this gives the biotech the ability to target these cancers without safety issues seen with currently approved CAR-Ts. The combination is not based on speculation only thus far, either; it has not only received Priority Medicines (PRIME) designation by the European Medicines Agency (EMA) for third-line or later treatment of testicular germ cell tumors, but has proven itself with early proof of concept data in addition to later-released updated data. The ability for BioNTech to use its mRNA technology to enhance CAR-Ts is only one aspect of the oncology pipeline it is moving forward.

Financials

According to the 6-K SEC Filing, BioNTech had $14.15 billion in cash and cash equivalents plus total trade receivables of $7.71 billion as of September 30, 2022. About $3.38 billion of the $7.71 billion trade receivables were received in cash as of October 15, 2022. As I noted above, BioNTech raised the lower end of its 2022 full-year financial guidance to include estimated Covid-19 vaccine revenues of $16.87 billion – $17.92 billion. For the 3-months ending September 30, 2022 it produced $3.65 billion in revenues for its Covid-19 vaccine.

Risks To Business

There are several risks that traders/investors should be aware of before investing in this biotech. I think the first risk to consider would be competition with respect to Comirnaty. It seems to be doing well so far in generating revenues in spite of competition from Moderna (MRNA) with Spikevax, but this may not always be the case.

A second risk to consider would be contracts to purchase doses of Comirnaty. That is, whether or not Governments around the globe continue to buy new doses of the Covid-19 vaccine, especially in the United States. Even then, the eventual move would be towards the private market instead. That may or may not be a good thing depending upon demand. That is, whether or not Comirnaty and other Covid-19 vaccines are in demand in the private market.

Another risk to consider would be with expansion opportunities I highlighted above. What do I mean by that? Well, the ongoing studies being deployed by BioNTech and Pfizer are experimental. There is no guarantee that adding an enhanced spike protein to BNT162b5 will result in increased efficacy. The final risk to consider would be with respect to BNT211, in that the combination of CAR-T targeting CLDN6 plus CARVac might not be enough to overcome the limitations observed with other CAR-T therapies.

Conclusion

The final conclusion is that BioNTech SE is a great long-term company to look into. While the ability to generate revenues with its partner Pfizer with Comirnaty might stop with respect to Government purchases, I believe that a shift to the private market might still allow it to produce Covid-19 vaccine revenues.

The thing about BioNTech is that it isn’t just focused only on advancing mRNA against Covid-19. It is also targeting other infectious diseases such as Malaria and influenza. It initiated a phase 1 study using BNT165b1 to be used against Malaria a few weeks ago. Not only that, but in collaboration with Pfizer, it is advancing a quadrivalent modified RNA (modRNA) influenza vaccine candidate in a phase 3 study. It also has many other mRNA candidates being developed to target multiple types of cancers. Plus, its pipeline is spread into other clinical candidates besides mRNA.

I already discussed about BioNTech SE’s possibility of advancing improved CAR-Ts. It also has an antibody drug candidate program against cancers, along with one small molecule drug against cancer. With the potential to expand the Covid-19 vaccine market with multiple trials/label expansions, plus the ability to possibly improve CAR-T treatments against solid tumors, these are the reasons why I believe BioNTech SE is a good long-term biotech to own.