Pipeline

At PhaseBio, we are committed to bringing innovation to the cardiovascular community, as exemplified by our pipeline of unique medicines.

Despite a declining trend over several decades, mortality rates for cardiovascular disease have been creeping up in recent years. The demographics of the patient population have also changed – rates of obesity and diabetes continue to rise, and now more women, non-smokers and younger individuals are presenting with cardiovascular disease. This makes the need for innovation that much more pressing.

Our novel cardiovascular therapeutic candidates may help meet this growing need. These include bentracimab (PB2452), an agent for the reversal of ticagrelor’s antiplatelet activity in major bleeding or to enable urgent surgery; and PB6440, an oral selective aldosterone synthase inhibitor for treatment-resistant hypertension.

Product Candidate

Preclinical

Phase 1

Phase 2

Phase 3

Commercial Rights

Bentracimab (PB2452)

Reversal of the Antiplatelet Activity of Ticagrelor

Phase 3

Commercial rights available in APAC and ROW

Upcoming Milestones

Biologics Licensing Application (BLA)
filing targeted for early Q4

PB6440

Treatment-resistant Hypertension

PRECLINICAL

Upcoming Milestone

Submission of Investigational New Drug application (IND) planned for first half of 2023

Partnering Opportunities

We leverage our ELP biopolymer technology to discover proteins and peptides that are scientifically or clinically promising, but where certain hurdles limit their potential therapeutic applications.

Pemziviptadil (PB1046)¹

Pulmonary Arterial Hypertension (PAH)

Phase 2b¹

Global commercial rights available

GLP2-ELP

Short Bowel Syndrome

Preclinical

Global commercial rights available

CNP-ELP

Achondroplasia

Preclinical

Global commercial rights available

Early Programs

PROPRIETARY LONG ACTING INJECTABLE RECOMBINANT BIOPOLYMERS
(Elastin-like Polypeptides – ELPs)

Phase 2b trial voluntarily stopped early due to COVID-19 impacts on manufacturing, associated drug supply and the rate of enrollment in the study; PhaseBio has elected to stop further development after a strategic review and will reprioritize resources towards pre-commercialization activities for bentracimab and the advancement of other pipeline programs, including PB6440 for resistant hypertension

BENTRACIMAB (PB2452)

A novel ticagrelor-reversal agent

Bentracimab (PB2452) is a novel recombinant human monoclonal antibody antigen-binding fragment, designed to reverse the antiplatelet activity of ticagrelor in the event of major bleeding or when urgent surgery is required. Ticagrelor is an antiplatelet therapy widely prescribed to reduce the rates of death, heart attack and stroke in patients with acute coronary syndrome (ACS), or who have previously experienced a heart attack. More recently, the FDA has approved a new indication for ticagrelor in patients with acute ischemic stroke or high-risk transient ischemic attack (TIA). The American College of Cardiology and American Heart Association guidelines recognize ticagrelor as the preferred antiplatelet therapy for ACS.

Ticagrelor binds to platelets to prevent them from forming blood clots that could restrict blood flow. As with other antiplatelet agents, patients on ticagrelor have an elevated risk of spontaneous bleeding. In addition, patients on ticagrelor who need urgent surgery cannot wait the recommended five days for the effects of ticagrelor to dissipate, meaning they are at increased risk of major bleeding during and after surgery. There are currently no other specific reversal agents approved or in clinical development for ticagrelor or any other antiplatelet drugs.

Bentracimab (PB2452) binds to ticagrelor with high affinity and specificity to reverse the antiplatelet activity of ticagrelor, as illustrated by data from the Phase 1 and Phase 2a clinical trials. We are currently conducting additional clinical trials to evaluate the safety and efficacy of bentracimab (PB2452).

For more information about our current clinical trials investigating bentracimab (PB2452), please visit our Clinical Trials page.

PB6440

An oral selective aldosterone synthase inhibitor for treatment of resistant hypertension

PB6440 is a novel selective aldosterone synthase inhibitor being developed for treatment-resistant hypertension. Despite the broad range of currently available antihypertensive therapies, approximately 10 million (20%) of drug-treated hypertension patients in the United States have not achieved target blood-pressure lowering while on three or more antihypertensive medications. These patients with treatment-resistant hypertension are at a significantly greater risk for major adverse cardiovascular events, including heart attack, stroke and heart failure, as well as peripheral artery disease and kidney failure.

The mineralocorticoid aldosterone is a critical regulator of fluid and electrolyte balance in the body and, as such, can play an important role in the development of high blood pressure or hypertension. Elevated aldosterone levels are associated with resistant hypertension, congestive heart failure and chronic kidney disease. Agents that block the action of mineralocorticoids at the receptor level, such as spironolactone, have been shown to lower blood pressure, including in patients with resistant hypertension.

However, use of these agents is limited by adverse side effects. Inhibition of the production of aldosterone through inhibition of the enzyme responsible for its synthesis, aldosterone synthase (CYP11B2), is an alternative approach to treatment of hypertension. However, development of aldosterone synthase inhibitors is challenging because of a closely related enzyme steroid 11β-hydroxylase (CYP11B1), which many potential compounds also inhibit. PB6440 has been shown to be a highly potent and selective inhibitor of aldosterone synthase and demonstrated a dose-dependent aldosterone reduction without a significant increase in 11-deoxycorticosterone or deoxycortisol in both rodent and primate models. The oral bioavailability and pharmacokinetic profiles appear suitable for once-daily dosing in humans. To date, no evidence of toxicity has been observed in either in vitro toxicity studies or in preclinical models.

We plan to submit an Investigational New Drug Application (“IND”) and initiate the first-in-human clinical trial in 2022.

Additional Discovery Programs

PhaseBio is leveraging our ELP biopolymer technology to evaluate additional preclinical and discovery-stage candidates. Our focus is on proteins and peptides that are scientifically or clinically validated, but where a suboptimal half-life, stability and delivery limit their potential therapeutic applications.

C-type natriuretic peptide

C-type natriuretic peptide (CNP) is a regulator of bone growth and can rescue defects in fibroblast growth factor 3 that cause achondroplasia resulting in dwarfism. Native CNP has a half-life of less than three minutes, limiting its use as a direct therapeutic. We are developing our CNP-ELP product candidate to deliver therapeutic levels of CNP with once weekly subcutaneous injections. In a mouse model, we observed a statistically significant effect on linear growth when our CNP-ELP product candidate was injected once every four days.

Glucagon-like peptide-2

Glucagon-like peptide-2 (GLP-2) stimulates growth of intestinal villi, increasing their ability to absorb nutrients. GLP-2 is a potential treatment for patients with short bowel syndrome, Crohn’s disease or mucositis in patients undergoing cancer treatment. Teduglutide, currently marketed under the brand name Gattex, is an FDA-approved therapy based on GLP-2 that requires daily injections. In animal models, our GLP-2-ELP product candidate provided sustained levels of GLP-2, resulting in greater efficacy than teduglutide with less frequent dosing.