Albireo Announces Positive Topline Data from Phase 1 Study of A3907

– First oral, systemic ASBT inhibitor was safe and well tolerated

– Secondary and exploratory objectives show favorable pharmacokinetics and systemic exposure, while providing target engagement signals

– Company on track to initiate planned adult liver disease Phase 2 study in 2022

BOSTON, Dec. 16, 2021 (GLOBE NEWSWIRE) — Albireo Pharma, Inc. (Nasdaq: ALBO), a rare liver disease company developing novel bile acid modulators, today announced positive topline results from its Phase 1 clinical trial of A3907, the first oral systemic apical sodium-dependent bile acid transporter (ASBT) inhibitor. The study achieved both primary and secondary objectives. Phase 1 study is a first-in-human, double-blind, single and multiple ascending dose study in healthy adult subjects to investigate the safety, tolerability, pharmacokinetics of orally administered A3907. A3907 was safe and well tolerated in this study at systemic exposures that demonstrated therapeutic benefits in preclinical models. With the potential to inhibit ileal, renal and hepatic ASBT, A3907 could provide the optimal balance of efficacy and tolerability in patients in multiple liver diseases.

The study met its primary objectives with data showing A3907 overall to be safe and well tolerated, with no serious adverse events (SAEs) or discontinuations due to treatment emergent adverse events (TEAEs). All TEAEs were mild, the most common were mainly abdominal symptoms such as loose stools, and all participants finished the trial protocol. No clinically significant effects in clinical chemistry, hematology, physical examinations or ECG. The study also met its secondary objectives with dose-related plasma exposure up to 81 mg dose, with no accumulation. Exposure levels were within the range that show effects in animal disease models. Single doses of A3907 showed dose proportional increases in plasma exposure up to 81 mg with no further increase at a dose of 162 mg. The study showed target engagement with 7alpha-hydroxy-4-cholesten-3-one (C4) increases and low-density lipoprotein cholesterol (LDL-C) reductions, with C4 increases indicating elevation in bile acid excretion, while LDL-C reduction indicating elevated synthesis of bile acids from cholesterol.

“The results from our Phase 1 study of A3907 show that the drug candidate is safe and well tolerated with favorable pharmacokinetics and high systemic exposure, giving us the greenlight to advance to a Phase 2 study,” said Jan Mattsson, Chief Scientific Officer of Albireo. “These results represent an exciting milestone in the development of this next generation bile acid modulators as we could potentially be offering physicians new treatments to treat liver diseases that could increase efficacy without sacrificing tolerability for patients.”

The Phase 1 trial was a randomized, double-blind, placebo-controlled, single and seven day multiple-dose study was conducted in 54 and 22, respectively, healthy subjects. Doses evaluated were 1-162 mg in the single ascending dose portion, and 9-67.5 mg in the multiple ascending dose portion. Primary objectives were safety and tolerability, secondary objectives were evaluation of pharmacokinetics, and there were multiple exploratory endpoints.

About A3907
A3907 is the first oral systemic apical sodium-dependent bile acid transporter (ASBT) inhibitor with high oral bioavailability that has potential to inhibit intestinal and renal bile acid reuptake as well as ASBT expressed by cholangiocytes. Due to high oral bioavailability, A3907 can inhibit ASBT in the intestine and kidney, with the potential to increase elimination of bile acids by both fecal and urinary excretion. By using dual pathway diversion of bile acids, next generation modulators like A3907 seek to increase efficacy without the dose limiting diarrhea seen with bile acid transport inhibitors today. A3907 is being developed for adult cholestatic liver diseases such as primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC).

The completed Phase 1 study of A3907 is a first-in-human, double-blind, single and multiple ascending dose study in healthy adult subjects to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of an A3907 oral formulation. In pre-clinical studies, A3907 showed high systemic exposure and increased level of urinary bile acid secretion in mice, and in a mice model of cholestasis and sclerosing cholangitis, A3907 decreased serum bile acids, and reduced plasma levels of transaminases as well as markers for cell damage and fibrosis.

About Cholestatic Adult Liver Diseases
Adult cholestatic diseases are a diverse group of disorders known for the appearance of jaundice, fatigue, pruritus and/or complications of cirrhosis. The most common adult cholestatic liver diseases are primary biliary cholangitis and primary sclerosing cholangitis. Primary biliary cholangitis is a chronic disease in which the bile ducts in the liver are slowly destroyed. When the bile ducts are damaged, bile can back up in the liver and sometimes lead to irreversible scarring of liver tissue (cirrhosis). Primary sclerosing cholangitis is a disease of the bile ducts where inflammation causes scars within the bile ducts. These scars make the ducts hard and narrow, gradually causing serious liver damage that leads to liver failure, repeated infections and tumors of the bile duct or liver.

About Albireo
Albireo Pharma is a rare disease company focused on the development of novel bile acid modulators to treat rare pediatric and adult liver diseases. Albireo’s lead product, Bylvay, was approved by the U.S. FDA as the first drug for the treatment of pruritus in all types of progressive familial intrahepatic cholestasis (PFIC), and it is also being developed to treat other rare pediatric cholestatic liver diseases with Phase 3 trials in Alagille syndrome and biliary atresia, as well as an Open-label Extension (OLE) study for PFIC. In Europe, Bylvay has been approved for the treatment of PFIC and has been submitted for pricing and reimbursement approval. The Company has also completed a Phase 1 clinical trial for A3907 to advance development in adult cholestatic liver disease, with IND-enabling studies moving ahead with A2342 for viral and cholestatic liver disease. Albireo was spun out from AstraZeneca in 2008 and is headquartered in Boston, Massachusetts, with its key operating subsidiary in Gothenburg, Sweden. The Boston Business Journal named Albireo one of the 2019 and 2020 Best Places to Work in Massachusetts. For more information on Albireo, please visit www.albireopharma.com.

Forward-Looking Statements
This press release includes “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements, other than statements of historical fact, regarding, among other things: the plans for, or progress, scope, cost, initiation, duration, enrollment, results or timing for availability of results of, development of Bylvay, A3907, A2342 or any other Albireo product candidate or program; the pivotal trial for Bylvay in biliary atresia (BOLD); the pivotal trial for Bylvay in Alagille syndrome (ASSERT); the Phase 1 trial for A3907; the IND-enabling studies for A2342; the target indication(s) for development or approval; the size, design, population, location, conduct, cost, objective, enrollment, duration or endpoints of any clinical trial, or the timing for initiation or completion of or availability or reporting of results from any clinical trial, including the long-term open-label extension study for Bylvay in PFIC, the BOLD and ASSERT trials, Phase 1 trial for A3907 and the IND-enabling studies for A2342; potential regulatory approval by and discussions with the FDA or EMA regarding our programs; or the potential benefits or competitive position of Bylvay or any other Albireo product candidate or program or the commercial opportunity in any target indication; Albireo often uses words such as “anticipates,” “believes,” “plans,” “expects,” “projects,” “future,” “intends,” “may,” “will,” “should,” “could,” “estimates,” “predicts,” “potential,” “planned,” “continue,” “guidance,” or the negative of these terms or other similar expressions to identify forward-looking statements. Actual results, performance or experience may differ materially from those expressed or implied by any forward-looking statement as a result of various risks, uncertainties and other factors, including, but not limited to: whether favorable findings from clinical trials of Bylvay to date, including findings in indications other than PFIC, will be predictive of results from other clinical trials of Bylvay; the timing for initiation or completion of, or for availability of data from, clinical trials of Bylvay, including BOLD and ASSERT, and the Phase 1 clinical trial of A3907, and the outcomes of such trials; Albireo’s ability to obtain coverage, pricing or reimbursement for approved products in the United States or Europe; delays or other challenges in the recruitment of patients for, or the conduct of, the Company’s clinical trials; and the Company’s critical accounting policies. These and other risks and uncertainties that Albireo faces are described in greater detail under the heading “Risk Factors” in Albireo’s most recent Annual Report on Form 10-K or in subsequent filings that it makes with the Securities and Exchange Commission. As a result of risks and uncertainties that Albireo faces, the results or events indicated by any forward-looking statement may not occur. Albireo cautions you not to place undue reliance on any forward-looking statement. In addition, any forward-looking statement in this press release represents Albireo’s views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Albireo disclaims any obligation to update any forward-looking statement except as required by applicable law.

Media Contact:
Colleen Alabiso, 857-356-3905, colleen.alabiso@albireopharma.com

Investor Contact:
Hans Vitzthum, LifeSci Advisors, LLC., 617-430-7578