BBIO - BridgeBio Pharma: FDA Submission Acromidis And Top Line Results On Deck

2024-01-11 17:19:01 ET

Summary

• BridgeBio Pharma, Inc. expects results from the phase 1/2 study, using gene therapy BBP-631 for the treatment of patients with congenital adrenal hyperplasia, in early 2024.
• The congenital adrenal hyperplasia treatment market is expected to reach $892 million by 2033.
• Potential FDA acceptance of regulatory application of acromidis for the treatment of patients with ATTR-CM, expected within 60 days after submission achieved December 5th of 2023.
• Results from phase 3 CALIBRATE study, using encaleret for the treatment of patients with autosomal dominant hypocalcemia type 1, expected in 2024.

BridgeBio Pharma, Inc. ( BBIO ) is expected to release results from its phase 1/2 study, using BBP-631 for the treatment of patients with congenital adrenal hyperplasia [CAH], in the early part of 2024. This is another catalyst for investors to look forward to, besides the potential for FDA approval of another drug known as Acromidis for the treatment of patients with transthyretin amyloidosis cardiomyopathy, also known as ATTR-CM. A New Drug Application [NDA] submission of this drug to the FDA for the treatment of this patient population had been submitted on December 5th of 2023. It is now in the hands of the FDA, because it has 60 days to decide upon whether or not the submitted regulatory application will be accepted for review. The thing is that Bridge Bio will compete against Pfizer ( PFE ) with its own ATTR-CM drug VYNDAMAX [tafamidis].

However, Bridge Bio does have the efficacy to back itself up, in that it is the only one to showcase an improvement of cardiovascular outcomes benefit in a prospective clinical trial in ATTR-CM patients. With the potential for FDA acceptance of the NDA submission of acromidis, plus results from the phase 1/2 study for using BBP-631 for the treatment of patients with CAH, I believe that investors could benefit from any potential gains made.

In addition, there is another shot on goal expected in 2024, which would be the release of results from the CALIBRATE trial. This phase 3 study is using encaleret for the treatment of patients with autosomal dominant hypocalcemia type 1 [ADH1]. It is expected that top line results from this study are expected in 2024. This is significant, because if this drug is eventually approved, it will become the first treatment option for these patients.

BBP-631 For The Treatment Of Patients With Congenital Adrenal Hyperplasia

The first program to go over involves the use of BBP-631, which is being developed for the treatment of patients with congenital adrenal hyperplasia [CAH]. Specifically, this is a gene therapy being advanced in an ongoing phase 1/2 study to treat these patients with CAH.

Congenital adrenal hyperplasia is a genetic disorder that affects a person's adrenal gland in the body. The adrenal gland is an important part of the body, because it is responsible for generating hormones that regulate metabolism, immune system and other functions. This is a large market opportunity for sure, because the congenital adrenal hyperplasia treatment market is expected to reach $892 million by 2033 .

What makes this gene therapy candidate, BBP-631 so special? That's because at the moment there are no therapies that target the underlying cause of the disease. This is designed to attempt to restore the body's ability to produce cortisol and aldosterone.

This is an important item to state, because at the moment no drugs approved or in clinical trials are able to do this for CAH patients. Cortisol is responsible for handling blood sugar levels [glucose], and then aldosterone is responsible for retaining salts in the kidneys and regulating blood pressure . If Bridge Bio can deliver promising results from this phase 1/2 study, then it could provide a whole new alternative way to treat this patient population. The thing is that CAH arises from these patients lacking an enzyme known as 21-hydroxylase. The goal of BB-631 is to restore the gene responsible for providing the necessary instructions to produce 21-hydroxylase. Without the CYP21A2 gene, there is a deficiency of the enzyme, thus the main cause of CAH.

The use of BB-631 is being explored in the ongoing phase 1/2 open-label, dose escalation study , which is expected to recruit up to a total of 25 patients who are to be treated with a couple of different doses. There is going to be preliminary data released from this study in the early part of 2024. However, such data, in my opinion, should be taken with a grain of salt. That is because the dose escalation portion data to be released is only going to entail a total of 6 patients that have been given BB-631 thus far.

Progress With Acromidis For Treatment Of ATTR-CM Is Being Made

As I stated above, the company has been able to file a New Drug Application [NDA] of acromidis to the FDA for the treatment of patients with transthyretin Amyloidosis cardiomyopathy [ATTR-CM]. This submission was made possible because of the primary endpoint being met in the phase 3 ATTRibute-CM study , whereby treatment with acromidis demonstrated a highly statistically significant primary endpoint of a WIN ratio of 1.8. This statistical significance was achieved with a p-value of p<0.0001. Thanks to this clinical finding, plus other findings, a submission was made to the FDA. Besides the 60-day waiting period on whether or not the agency will accept this application of acromidis, there are already plans being made to submit several other regulatory applications to other territories across the globe in 2024.

Should such submissions happen, then these would be additional catalysts to look forward to. The thing is that even if acromidis is ultimately approved by the FDA and other regulatory authorities, then it will have to go up against Pfizer's approved drug known as VYNDAMAX [tafamidis].

It remains to be seen whether or not Bridge Bio's acromidis will be able to take market share from Pfizer's drug, but there is one possible advantage it might be able to tout. That is, acromidis might be the only drug for ATTR-CM patients capable of demonstrating cardiovascular outcomes benefit in a prospective clinical trial for them. However, tafamidis is entrenched very well in this market space and might be hard to go against. Despite that, half of doctors surveyed stated that they would be willing to first try patients out with acromidis. Of course, that's if this drug is eventually approved by the FDA. Thus, there is a chance that acromidis may fare well also.

Financials

According to the 10-Q SEC Filing , Bridge Bio had cash, cash equivalents, and short-term investments of $521.9 million as of September 30th of 2023. The thing about this biotech is that it will definitely need to raise cash in 2024 to keep its pipeline funded. That's because it has needed to enact several financial instruments in 2023 to keep itself funded. Not only that, but it expects that its cash on hand will be enough to fund its operations for at least the next 12 months from the date of the 10-Q SEC filing, which was filed on November 2, 2023. However, it may not need to announce new financial transactions, especially since it already has several ones it can already tap into that had been filed in 2023.

That's because it has been able to generate cash through several means as I previously stated. For instance, in March of 2023 it raised a total of $143 million in net proceeds from a follow-on offering, whereby a total of 8,823,530 shares of its common stock were sold a public offering price of $17 per share. In addition, a Shelf Registration filing to sell up to $450 million worth of shares of stock from time to time was enacted. This "at-the-market" offering program was used thus far, however, not much of it.

As of September 30th of 2023, net proceeds of about $65 million were generated. Thus, there is roughly $384 million worth of common stock left pursuant to this ATM agreement. Lastly, a private placement agreement was entered into in September of 2023, whereby total net proceeds of $241.3 million was generated.

Risks To Business

There are several risks that investors should be aware of before investing in Bridge Bio. The first risk to consider would be with respect to the New Drug Application [NDA] of acromidis for the treatment of patients with ATTR-CM. That's because even though this regulatory application had been submitted, there is no assurance that it will end up being accepted for review.

A second risk to then consider would be if acromidis is eventually given U.S. marketing approval for the treatment of this patient population. As I stated briefly above, Pfizer has already been able to receive FDA approval of its ATTR-CM drug known as VYNDAMAX. It is not going to be easy for Bridge Bio to eventually steal market share from it, even if acromidis is ultimately given the green light.

A third risk to consider would then be with respect to the release of topline results from the ongoing phase 1/2 study, which is using gene therapy BBP-631 for the treatment of patients with congenital adrenal hyperplasia [CAH]. The company is taking a huge risk here, because the goal is to use a curative therapy to not only treat this disorder, but to target the underlying cause of it. That is, it intends to be able to cure the deficiency of the enzyme 21-hydroxylase observed in this patient population by restoring the function of the CYP21A2 gene. There is no guarantee that overcoming this challenge will be possible and a failure here would mean a huge setback for this program and for these patients.

In essence, this would allow for patients to avoid daily steroid use , which has been used for more than 50 years. A fourth risk would be the release of results from the phase 3 CALIBRATE trial, which is using encaleret for the treatment of patients with ADH1. These results are expected at some point in 2024 and there is no guarantee that the primary endpoint of this trial will be met with statistical significance.

The fourth and final risk to consider would be with respect to the financial position that it is in. As I stated before, it projects that it only has enough cash on hand for at least the next 12 months. Thus, it is likely going to need to raise additional cash in the coming months.

Conclusion

There is an opportunity here, because there is a major catalyst that is rapidly approaching. This would be upon the possibility of the FDA accepting the regulatory NDA of acromidis for review. Acromidis is a drug which is being advanced for the treatment of patients with ATTR-CM. The agency has roughly 60 days from the time of submission [December 6th of 2023] to decide if it wants to accept the filing for review.

The other two catalysts coming about from its pipeline are also ideal as well. That's because other results in 2024 are expected from studies using encaleret for patients with ADH1 and then BBP-631 for the treatment of patients with CAH. These are additional shots on goal, and if these trials are successful, then I believe that these could possibly cause the stock price to trade higher.

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