CVAC - BioNTech: Able To Tap Into High Medical Need PD-L1 Refractory NSCLC Market

2023-05-22 17:43:28 ET

Summary

• BioNTech SE has initiation of a phase 3 study using BNT316 as a monotherapy for PD-1/PD-L1 refractory non-small cell lung cancer patients that is expected to take place in 2023.
• Updated results from the expansion cohort from phase 1/2 study using BNT316 for the treatment of non-small cell lung cancer patients will be presented at ASCO June 2 - 6 of 2023.
• It is expected that the global non-small cell lung cancer market could reach $36.9 billion by 2031.
• It is estimated that Comirnaty vaccines revenues could be $5.4 billion in 2023.

BioNTech SE ( BNTX ) is a good speculative biotech play to look into. That is because it is already producing revenues from a partnership with Pfizer Inc. ( PFE ) in selling the Covid-19 vaccine Comirnaty. Matter of fact, it has reiterated that it will produce $5.4 billion in revenues in 2023 for this vaccine.

However, BNTX can't solely only rely on being a good long-term biotech if it doesn't expand its horizons. It is doing well to establish a very large pipeline, and this is proven with the amount of products it is focusing on. It has 27 phase 1 studies, 10 phase 2 studies, and one phase 3 study. What I want to zero in on is a huge market opportunity that is largely untapped. By this, I mean the PD-L1 refractory non-small cell lung cancer [NSCLC] market.

BioNTech and its partner OncoC4 are gearing up to initiate a phase 3 study using a next generation anti-CTLA-4 antibody BNT316 [previously ONC-392] as a monotherapy for the treatment of patients with NSCLC who progress after PD-1/PD-L1 treatment. Another reason why I want to bring up BNT316 is because it is an anti-CTLA-4 antibody drug, which may allow for higher dosing than prior generation anti-CTLA-4 drugs. This could mean enhanced efficacy for this patient population. The collaboration involves the potential to use BNT316 alone or in combination with other checkpoint inhibitors to target various types of solid tumors.

The final reason why I believe that it is important to bring up this program is because there also is a catalyst opportunity for investors to look forward to in the coming weeks as well. It is expected that BioNTech will present updated results from an expansion cohort from the ongoing phase 1/2 study using BNT316 as a monotherapy for the treatment of patients with NSCLC. Results from this mid-stage study are expected to be presented at the upcoming American Society of Clinical Oncology [ASCO] Annual Meeting to be held from June 2nd - June 6th of 2023.

With the potential to tap into a high medical need NSCLC market, plus a few catalysts approaching in 2023, these are the reasons why I believe that BioNTech is a good speculative biotech play to look into.

First Phase 3 Study Could Provide Ability To Use Next Generation Anti-CTLA-4 Monoclonal Antibody

As I noted in the beginning above, BioNTech has an extensive pipeline, but what I find most intriguing would be the advancement of a partnered candidate by the name of BNT316 in a phase 3 study. That is, the company formed a partnership with a private pharmaceutical company by the name of OncoC4 to advance its next-generation anti-CTLA-4 monoclonal antibody alone or in combination with other anti-PD-[L]-1 antibodies to target patients with solid tumors. Under the terms of the agreement, OncoC4 was to receive an upfront payment of $200 million and then is eligible to earn development, regulatory and commercial milestone payments based on this deal. In addition, OncoC4 is to also receive double-digit tiered royalties on net sales for any products that are ultimately marketed.

The first target indication under this partnership is PD-1/PD-L1 refractory non-small cell lung cancer patients. Lung cancer , as the name suggests, is a type of cancer that forms in the lungs of a patient. It is where cells start to grow out of control, leading to the formation of solid tumors.

Why is this a good market for both BioNTech and its partner to go after? There are several reasons why this is the case. The first reason is that 80% to 85% of lung cancers are NSCLC. The second reason is because it is a large market opportunity to go after. It is expected that the global non-small cell lung cancer market could reach $36.9 billion by 2031 . The third reason is because the specific population being targeted are such NSCLC patients who don't respond to current PD-1/PD-L1 therapies like Keytruda or Opdivo. This is the case either because of cancer resistance, or the therapy just isn't strong enough to deliver a durable long-lasting response.

A major problem is that PD-1/PD-L1 therapies, such as currently approved therapies, only benefit NSCLC patients who have high PD-L1 tumor proportion scores [TPS]. For instance, such an example that can be gleamed over would be what occurred in the phase 1 KEYNOTE-001 study. With NSCLC patients who were previously given a PD-L1 inhibitor, along with a TPS ? 50%, they had a median overall-survival of 15.4 months. Pretty good durable response, right? Well, patients with a PD-L1 TPS that ranged between 1% and 49% only had a median overall survival of only 8.5 months. The premise here is that TPS was used as a biomarker to predict clinical benefit.

The bottom line here is that while checkpoint inhibitors like Keytruda and Opdivo are used alone or in combination with chemotherapies as first-line treatments, not all patients benefit from them. Thus, the potential here is that BNT316 will not be in direct competition with checkpoint inhibitors, but to target a NSCLC patient population who do not benefit from them.

The phase 3 study using BNT316 alone as a monotherapy in PD-1/PD-L1 refractory NSCLC patients is expected to be initiated in 2023. Again, the hope here is to provide clinical benefit for those who progress when given checkpoint inhibitors. Besides this phase 3 study initiation being a catalyst to look forward to, there is another rapidly approaching catalyst. That is, BioNTech and its partner OncoC4 plan to present data from an expansion cohort which is testing the use of BNT316 as a monotherapy in NSCLC patients from an ongoing phase 1/2 clinical study. Such data is going to be presented at the upcoming American Society of Clinical Oncology [ASCO] Annual Meeting to be held in Chicago from June 2 - 6 of 2023.

The use of this drug has been in development for several years now. Both companies are not advancing BNT316 into phase 3 clinical testing without some proof of concept. They are doing so because of clinical results that were released at Society for Immunotherapy of Cancer [SITC] in both 2022 and 2021. It was shown that this drug worked well alone as a monotherapy or in combination with Keytruda with advanced solid tumors. In particular either treatment option did well for patients who progressed on prior PD-1 and CTLA-4 therapies. Results released at the 2022 SITC meeting , showed that ONC-392 in combination with pembrolizumab [Keytruda] from the PRESERVE-001 study, achieved a 30% objective response rate [ORR] for these metastatic cancer patients.

With such data obtained from both of these cohorts, this is the reason why both BioNTech and OncoC4 decided to advance BNT316 into a phase 3 clinical study. Again, this study is expected to start soon in 2023. What gives confidence for potential success in my eyes, is that they are taking a purely monotherapy approach in targeting this PD-1/PD-1 refractory NSCLC patient population. It will not be combining a checkpoint inhibitor with BNT316 to treat these patients.

Potential Expansion Opportunities With Next Generation Anti-CTLA-4 Monoclonal Antibody

The hope is that BioNTech and its partner OncoC4 deliver for these NSCLC patients who don't benefit from checkpoint inhibitor therapy. However, with the partnership I noted above, it doesn't just end with NSCLC patients only. The goal is to eventually use this next anti-CTLA-4 antibody BNT316 along as a monotherapy or in combination with other checkpoint inhibitors to treat patients with various types of solid tumors. Thus, if the phase 3 study ultimately establishes proof of concept, then this drug could be applied towards many other solid tumor indications. The potential to expand upon the use of BNT316 goes even further than what I just noted here. While the partnership with OncoC4 deals with the use of BNT316 alone or with PD-1 inhibition for solid tumors, it doesn't include anything outside of this.

What do I mean? Well, BioNTech wants to attempt to develop combinations with BNT316 against solid tumors outside of PD-1 inhibition. For instance, to combine BNT316 together with its other immuno-oncology products in its pipeline. If this happens, then it will be solely developed by BioNTech on its own. Thus, as you can see, it has many different approaches it can take towards advancing BNT316 for several types of solid tumors. It is not just limited to only BNT316 alone as a monotherapy or only BNT316 together with PD-1 inhibition.

Next Generation Anti-CTLA-4 Monoclonal Antibody Mechanism Of Action Is Differentiated

While BNT316 is an anti-CTLA-4 monoclonal antibody, it does have some advantages in being a next generation type. Before diving into the differences, it is important to note what an anti-CTLA-4 drug is responsible in doing. The CTLA4 protein, which acts as immune checkpoint, blocks T-cell immune responses to fight cancer cells. It also blocks the ability for the body's immune system to kill off cancer cells.

What BNT316 is set to do is to preserve T-cell immune function [kill cancer cells it recognizes] and to also enhance anti-tumor activity. Another function is the ability to target/delete immunosuppressive T-cells [regulatory T-cells or Tregs] in the microtumor environment, while leaving Tregs in healthy human tissues alone. Thus, being a next generation anti-CTLA-4 drug. The improvement in safety profile of BNT316 [Tregs not being targeted in healthy human tissue cells] might allow for higher dosing and longer duration of treatment. It was shown in preclinical testing that this drug showed improved cancer immunotherapeutic effect [CITE] while at the same time reducing immunotherapy-related adverse events [irAE].

It is hard to say for sure if higher dosing being done or longer treatment duration results in better therapeutic benefit compared to other anti-CTLA-4 drugs, but this is something definitely worth exploring further. The logic here is that while ant-CTLA-4 drugs have been used for more than a decade as a cancer therapy, it doesn't mean that its therapeutic profile can't be enhanced upon. I would say that the updated expansion cohort results, to be released from the phase 1/2 study using BNT316 as a monotherapy for NSCLC at ASCO, will provide some evidence if such a next generation anti-CTLA-4 drug is capable of improving the therapeutic profile for this class of drugs for the targeting of solid tumors.

Financials

According to the 6-K SEC Filing , BioNTech SE had cash , cash equivalents as well as security investments of $12.14 billion and $726 million respectively. In addition, $3.96 billion was received after the end of this reporting period with respect to gross profit share based on the contract with Pfizer for Covid-19 sales of Comirnaty.

This biotech is different than most others in that is already generating sales because of the marketed Covid-19 vaccine with Pfizer. Matter of fact, it estimates that it will generate $5.4 billion in revenues in 2023 in Covid-19 vaccine sales. This will be less than in 2022, because Covid-19 vaccine sales have started to decline.

However, I believe that the longevity of this biotech will be on advancing many of its other pipeline products in immuno-oncology. Especially, with the advancement of BNT316 into a phase 3 study, which is expected to start soon in 2023.

Risks To Business

There are several risks that traders/investors should be aware of before investing in BioNTech. The first risk to consider would be with respect to the use of BNT316 for the treatment of patients with PD-1/PD-L1 refractory NSCLC, which is going to have a phase 3 study initiated in 2023. While prior data suggests great potential in BNT316 being used as a monotherapy for the treatment of this patient population, there is no guarantee that the phase 3 study will achieve a successful outcome upon data release.

A second risk to consider would be with respect to the possible expansion opportunities I highlighted above. There is no guarantee that putting BNT316 in combination with PD-1/PD-L1 inhibitors or other BioNTech immuno-oncology candidates in the pipeline, will result in positive data.

A third risk to consider would be dealing with the estimated sales of Covid-19 vaccine Comirnaty. While the estimate is that BioNTech will obtain $5.4 billion in revenues in 2023 for this vaccine, there is no guarantee that it will do so.

Speaking of Covid-19 vaccine sales, there is another risk to consider here. This relates to several lawsuits of biopharmaceutical companies claiming that their patents were infringed upon with respect to the development of Comirnaty. It, along with its partner Pfizer, have pending lawsuits from Moderna, Inc. ( MRNA ), CureVac N.V. ( CVAC ), Alnylam Pharmaceuticals, Inc. ( ALNY ) and Arbutus Biopharma Corporation ( ABUS ) all relating to Comirnaty vaccine sales. Moderna, CureVac and Alnylam lawsuits were filed in 2022. While the Arbutus lawsuit was filed in 2023. It's uncertain what will happen with respect to each of these lawsuits, but BioNTech states that it will vigorously defend itself.

My feeling is that legal proceedings are uncertain, thus it's hard to say what will happen with respect to these lawsuits in the end. Not only that, such lawsuits could take years to conclude. Regardless, these are risks that must be considered before investing in this biotech. Still, I believe that the long-term potential for BioNTech will be with respect to its immuno-oncology pipeline going after solid tumor indications. Sales of Comirnaty should be considered a bonus, but not part of a long-term investment strategy.

Conclusion

The final conclusion is that BioNTech SE is a good speculative biotech play to look into. That's because both in 2021 and in 2022 it has established preliminary proof of concept in being able to use BNT316 in being able to treat patients alone as a monotherapy or in combination with Keytruda in patients with metastatic cancer, particularly in those who progressed on prior immunotherapies targeting PD-1 and CTLA-4.

What's even more encouraging is that traders/investors have a catalyst opportunity to look forward to. BioNTech along with its partner OncoC4, will present updated results from its expansion cohort from the ongoing phase 1/2 study using BNT316 as a monotherapy for the treatment of patients with NSCLC. These results are going to be released as a poster presentation at the upcoming American Society of Clinical Oncology [ASCO] Annual Meeting to be held from June 2nd - June 6th of 2023.

In addition, there are several expansion opportunities as I highlighted above. This is with respect to combining BNT316 with checkpoint inhibitor therapies or with BioNTech's own immuno-oncology drugs in its pipeline. It is still expected to generate substantial Comirnaty vaccine sales with its partner Pfizer, but I wouldn't base my entire investment thesis on this alone.

I believe that the future of BioNTech SE will depend upon its ability to be successful with BNT316 and other immuno-oncology products against solid tumors. With the potential to tap into a high medical need NSCLC market, plus a few catalysts approaching in 2023, these are the reasons why I believe that BioNTech SE is a good speculative biotech play to look into.

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