PFE - BridgeBio Pharma: Positive ATTR-CM Treatment Data Leads To Other 2023 Catalysts

2023-07-17 18:42:44 ET

Summary

• Primary endpoint met in BridgeBio Pharma, Inc.'s phase 3 ATTRibute-CM study, which used acoramidis for the treatment of patients with transthyretin amyloid cardiomyopathy; NDA filing expected before end of 2023.
• Results from the phase 3 ATTRibute-CM study were accepted as a late-breaker presentation for the European Society of Cardiology Congress 2023, taking place August 25 to August 28 of 2023.
• Results from the phase 3 CALIBRATE study, using encaleret for the treatment of patients with autosomal dominant hypocalcemia type 1 [ADH1] are expected by 1st half of 2024.
• Other catalysts expected in 2023 are the initiation of a global phase 3 registration study using BBP-418 for LGMD2I, and data readout from a phase 1/2 study using BP-631 for CAH.

BridgeBio Pharma, Inc. ( BBIO ) had made great progress as it relates to its drug acoramidis. That is, it posted positive results from its phase 3 ATTRibute-CM study, which used acoramidis to treat patients with transthyretin amyloid cardiomyopathy [ATTR-CM]. Why I believe that investors might be able to capitalize on additional potential gains here is because the release of this positive data sets up other catalysts to come within a 1-year period. For instance, with the primary endpoint of this phase 3 study being met, it expects to file a New Drug Application [NDA] of acoramidis to the FDA before the end of 2023. Not only that, but regulatory filings for additional applications of acoramidis are expected in 2024.

The use of acoramidis for ATTR-CM isn't the only phase 3 program that it has. It is evaluating the use of encaleret for the treatment of autosomal dominant hypocalcemia type 1 [ADH1] in the ongoing phase 3 CALIBRATE registrational trial. It is expected that results from this phase 3 study with encaleret are going to be released in the 1st half of 2024. Another, smaller catalyst to make note of would be that the clinical data from the phase 3 ATTRibute-CM study was accepted as a late-breaker presentation for the annual meeting of the European Society of Cardiology [ESC] Congress 2023 , which is to be held between August 25 to August 28 of 2023. Plus, there are going to be a few other catalysts besides these ones to be released in 2023 as well.

Positive Data Leads To New Hope For Increasingly Recognized Cause Of Heart Failure

As I stated above, BridgeBio achieved positive results from its phase 3 ATTRibute-CM study, which used its small molecule drug acoramidis for the treatment of patients with transthyretin amyloid cardiomyopathy [ATTR-CM]. ATTR-CM occurs as a result of a few actions that occur within a person's body. What happens first is that the liver produces faulty transthyretin [TTR] proteins, which build up in clumps [known as fibrils]. Such fibrils start to build up on the hearts' left ventricle, which becomes stiff/weak and thus makes it difficult for your heart to pump blood out to the rest of the body.

One major issue with ATTR-CM is that it can lead to heart failure. This is where a treatment option like acoramidis comes in, in that it was designed to mimic a naturally occurring variant of the TTR gene, known as T119M. Why is such a variant important? That's because it is known as a "rescue mutation," which is capable of being able to reduce or minimize ATTR. In essence, acoramidis is able to stabilize TTR. Not only that, but in prior preclinical and clinical studies, it was able to achieve twice the stabilization of other already-marketed TTR stabilizers.

The phase 3 ATTRibute-CM phase 3 Trial was a double-blind, placebo-controlled study of the safety and efficacy of acoramidis in patients with symptomatic Transthyretin Amyloid Cardiomyopathy [ATTR-CM]. About 632 patients were recruited and randomized to receive either acoramidis or placebo twice daily and were evaluated for a 30-month period. The primary endpoint of this study looked at a hierarchical analysis prioritizing in order of several measures such as: All-cause mortality, then frequency of cardiovascular-related hospitalization, then change from baseline in NT-proBNP, then change from baseline in 6-minute walk distance. This primary endpoint was met with statistical significance with a Win Ratio of 1.8 and p-value of p<0.0001.

In addition, as highly statistically significant relative risk reduction of 50% on frequency of cardiovascular-related hospitalization was also achieved, with a p-value of p<0.0001. Acoramidis was also able to achieved statistical significance with respect other endpoint markers in ATTR-CM patients such as: Morbidity, function and Quality of life [QOL]. The best part about this data is that there were no safety signals observed for patients who received treatment with acoramidis.

While significant gains have been made on the release of the primary endpoint being met with the phase 3 ATTRibute-CM study, it doesn't mean that there aren't any catalysts left for investors to capitalize on. For instance, this positive data brings about the ability for BridgeBio to file an NDA to the FDA of acoramidis for the treatment of patients with ATTR-CM before the end of 2023. Thus, another batch of catalysts would be regulatory filings of acoramidis in ATTR-CM for several other territories.

Another catalyst to consider, as it relates to this program, would be the late-breaker presentation of data from the phase 3 ATTRibute-CM study. Data from this late-stage study is going to be presented at the upcoming European Society of Cardiology [ESC] Congress 2023, which is to be held between August 25 to August 28 of 2023.

Financials

According to the 10-Q SEC Filing , BridgeBio Pharma had cash, cash equivalents, marketable securities and restricted cash of $467 million as of March 31, 2023. The reason for the cash on hand is because of two financial transactions that were achieved. One of the financial transactions done was the net proceeds of $143 million received from the follow-on public offering. The second financial transaction done was the proceeds from the common stock issuance under ESPP and stock option exercises of $2 million.

I believe that this biotech may have to raise cash again. Why is that? That's because it believes that it has enough cash to fund its operations for at least the next 12 months from the date of the 10-Q SEC Filing , which was filed on May 4, 2023. This doesn't give a lot of cash runway, especially now that the company will need to file for regulatory approvals in several territories for acoramidis.

Plus, it might have to start thinking about pre-commercialization activities as well. With the stock trading higher by as much as 80% it is highly likely that it will raise cash almost immediately, maybe even within the next few days. It can either do this through another public offering or it can use its Open Market Sales Agreement. This is an Open Market Sale Agreement it made with Jefferies LLC and SVB Leerink LLC to provide for the offering, issuance and sale of up to an aggregate offering price of $350 million of its common stock. As of March 31, 2023, it is still able to tap into this agreement and sell up to $345 million of its common stock should it choose to do so.

Risks To Business

There are several risks that investors must be aware of before investing in BridgeBio Pharma. The first risk to consider would be with respect to the recent positive results it achieved with respect to the phase 3 ATTRibute-CM study. That's because it expects to file an NDA of acoramidis for ATTR-CM before the end of 2023 and then subsequent regulatory filings for other territories thereafter. There is no guarantee that the FDA or other regulatory agency around the globe will either accept the filings or grant marketing approval in their respective territories.

A second risk to consider would be with respect to ongoing competition in this particular space . Even if acoramidis is ultimately approved, it is not alone in targeting this specific market. That's because it may have to go up against Alnylam Pharmaceuticals ( ALNY ) with patisiran and then Pfizer ( PFE ) with Vyndamax [tafamidis]. Vyndamax is already approved by the FDA for the treatment of patients with ATTR-CM. Now, with respect to patisiran, it highly depends upon what happens with review of this drug. Alnylam submitted and the FDA had accepted a supplemental New Drug Application [sNDA] of patisiran for the treatment of ATTR-CM patients. A PDUFA date of October 8, 2023 had been established for review of this drug for this patient population. Should it receive FDA approval, then this would be another competitor that BridgeBio would have to compete against.

A third risk to consider would be with respect to another candidate in the pipeline, which is encaleret. This particular drug is being explored in the ongoing phase 3 CALIBRATE for the treatment of patients with autosomal dominant hypocalcemia type 1 [ADH1]. Results from this late-stage registrational study are expected to be released in the 1st half of 2024 and there is no guarantee that the primary endpoint of this study will be met.

The fourth and final risk to consider would be the financial position BridgeBio Pharma, Inc. is in. As stated above, it believes it only has enough cash for 12 months from the date of its 10-Q SEC Filing. With the stock price rising higher by around 80% or so, it is highly likely that it may enact a cash raise immediately, maybe even within the next few days.

Conclusion

BridgeBio Pharma, Inc. was able to achieve the primary endpoint from the phase 3 ATTRibute-CM study, which used acoramidis for the treatment of patients with transthyretin amyloid cardiomyopathy [ATTR-CM]. Having said that, this leads to a few other catalysts for investors to look forward to, such as late-breaking presentation of this data at the upcoming ESC Congress in August of 2023. Plus regulatory filing of acoramidis to the FDA before the end of 2023 and then subsequently submissions to other territories in 2024. Lastly, the company also has another phase 3 study it is working on. This would be the evaluation of encaleret for the treatment of autosomal dominant hypocalcemia type 1 [ADH1] in the ongoing phase 3 CALIBRATE study.

It is expected that results from this late-stage registrational study are going to be released in the 1st half of 2024. There are some other catalysts expected from some other programs in the pipeline as well. For instance, there is a plan to initiate a global phase 3 registration study using BBP-418 for the treatment of limb-girdle muscular dystrophy type 2I [LGMD2I] in 2023. Then, there is a data readout from a phase 1/2 study using BP-631, which is being developed for the treatment of patients with congenital adrenal hyperplasia [CAH]. Results from this study are expected to be released before the end of 2023. With the primary endpoint being met in the phase 3 ATTRibute-CM study with acoramidis, plus many other catalysts expected in 2023, I believe that investors might be able to capitalize on any other possible gains made here by BridgeBio Pharma, Inc.

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