ALBO Albireo Pharma Inc

Albireo Pharma, Inc. (Nasdaq: ALBO), a clinical-stage rare liver disease company developing novel bile acid modulators, today announced new data in nine accepted abstracts to be presented at EASL International Liver Congress™ 2021 on June 23 – 26. Data being presented demonstrate Albireo’s leading position in the science of bile acid modulation with further evidence of efficacy and tolerability of Bylvay (odevixibat), as well as advancement in the characterization of A3907 in adult liver disease. Highlights from the Phase 3 PEDFIC studies show further evidence of a sustained and durable effect with Bylvay, while also showing improvements in sleep, growth and hepatic parameters in patients with progressive familial intrahepatic cholestasis (PFIC). The Company will also have a presentation and poster on Phase 1 candidate, A3907, with pre-clinical data showing efficacy on markers of cholestatic disease.

“We are pleased to follow-up the statistically significant PEDFIC Phase 3 results with additional detailed data that reinforces the rapid, as well as longer term benefits of Bylvay for patients with PFIC,” said Ron Cooper, President and Chief Executive Officer of Albireo. “The PEDFIC program is the largest body of prospective data collected in patients with PFIC and provides further proof of Albireo’s scientific expertise in applying bile acid modulation to treat rare cholestatic liver diseases.”

Bylvay Treatment in Pediatric Liver DiseasesBylvay is a potent, once-daily, non-systemic ileal bile acid transport inhibitor (IBATi) currently being developed for the treatment of PFIC, biliary atresia, and Alagille syndrome. PEDFIC 1 was the first and largest, global, pivotal Phase 3 study conducted in PFIC, which evaluated the efficacy and tolerability of Bylvay in reducing pruritus and serum bile acids in a randomized, double-blind, placebo-controlled trial, and PEDFIC 2 is a long-term, open-label Phase 3 extension study. Data being presented includes a pooled analysis of 77 patients treated with Bylvay. Key findings include:

• Affirms Improvement in Clinically Meaningful Endpoints: Patients with PFIC treated with Bylvay for up to 48 weeks experienced clinically meaningful effects on serum bile acids (sBAs), pruritus, growth and sleep parameters.
  • At baseline, sBAs score was 250 μmol/L and pruritus score was 2.9. Four weeks after starting Bylvay, sBAs had decreased by 88 μmol/L and pruritus score decreased by 0.7. At the end of the analysis period, sBAs had decreased from baseline by 213 μmol/L in patients with available data and pruritus score dropped by 1.4.
  • Height Z scores increased from –1.9 at baseline to –0.8 at week 48 and similar improvements were observed for weight Z scores (baseline: –1.1; week 48: –0.0).
  • Bylvay-treated patients had changes from baseline to weeks 37–48 in observer-reported percentage of days seeing blood due to reductions in scratching (–25%), needing help falling asleep (–52%), needing soothing (–51%) and sleeping with caregiver (–40%).
  • The observed safety and tolerability profile of Bylvay was consistent across studies, treatment groups and doses. No drug-related serious adverse events were reported in either PEDFIC 1 or PEDFIC 2. One patient in PEDFIC 1 and 3 patients in PEDFIC 2 treated with Bylvay withdrew due to an adverse event. There were low numbers of gastrointestinal adverse events; treatment-related diarrhea/frequent bowel movements was reported in 10% of Bylvay treated patients in PEDFIC 1 and 5% of placebo-treated patients.
• Rapid and Durable Effect: Results of this pooled analysis in children with PFIC from two Phase 3 studies show that Bylvay was associated with rapid reductions in serum bile acid levels and improvements in pruritus severity, with durable clinical benefits sustained through 48 weeks of treatment.
  • By week 4, 31% of patients treated with Bylvay were serum bile acid responders. At weeks 46−48, 67% of patients were serum bile acid responders.
  • From baseline to week 4 and baseline to week 48, the proportion of positive pruritus assessments at the patient level with Bylvay treatment was 54% and 66%, respectively.
  • A rapid reduction in autotaxin levels was observed by week 4, with a mean change from baseline in autotaxin with Bylvay treatment of −712 ng/mL. Continued reduction in autotaxin was observed at 48 weeks, with a mean change from baseline of −2,298 ng/mL.
  • Mean change from baseline in plasma C4 with Bylvay treatment was 10 ng/mL at week 4 and 31 ng/mL at 48 weeks.
• Responders Showed Effects on Cholestasis-Related Parameters: Patients with PFIC who responded to Bylvay treatment had sustained improvements in cholestasis-related parameters over 48 weeks that were not observed to the same extent in treatment non-responders.
  • Rates of sBA responders and sBA or pruritus responders were 31% and 57%, respectively, at weeks 0−24, 48% and 60% at weeks 25−36, and 59% and 65% at weeks 37−48.
  • Among all Bylvay-treated patients, mean change from baseline (CFB) to week 48 in alanine aminotransferase (ALT) was –82 U/L and total bilirubin –18 μmol/L.
• Improvement in Multiple Sleep Parameters: Patients with PFIC and Bylvay treatment response had substantial improvements in caregiver- and clinician-reported sleep parameters; these effects occurred rapidly and continued over time.
  • Mean decreases in caregiver-reported percentage of days with scratching associated with bleeding, needing help falling asleep, and needing soothing were greater among responders vs. non-responders.
  • At 48 weeks, clinicians and caregivers reported that ≥88% of responders had moderately or very much better sleep since starting Bylvay.
• Pretreatment Serum Bile Acid Parameters and Predictability of Response: Response to Bylvay treatment in patients in PEDFIC 1 was not associated with pretreatment serum concentrations of total, primary or secondary bile acids, or with C4 levels.
  • Among the 42 patients treated with Bylvay in PEDFIC 1, 32 used concomitant UDCA, while 10 did not.
  • Overall, 40 patients had available UDCA concentration data. In patients who used UDCA, the median (mean) baseline UDCA concentration was 55.6 (76.0) μmol/L. In those who did not use UDCA, the median (mean) baseline UDCA concentration was 0.2 (16.9) μmol/L

A3907 in Adult Liver DiseaseCompany to present an oral and poster presentation on data from our preclinical studies of A3907 in adult liver disease, which is currently in an ongoing Phase 1 study. A3907, the first oral systemic apical sodium-dependent bile acid transporter (ASBT) inhibitor in clinical studies, being developed for adult cholestatic liver diseases such as primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC). A3907 has the potential to significantly change the bile acid transporter approach in adult liver diseases by diverting bile acids from the liver through fecal and urinary excretion. Following successful preclinical studies demonstrating the unique mechanism of action, data to be presented is from two models that show the impact of A3907 in models of cholestasis and NASH. The first study was aimed to investigate the effect of A3907 in the Mdr2 knockout mouse model of cholestatic liver injury and sclerosing cholangitis. The objective of the second study was to investigate the effects of A3907 in obese diet-induced mouse models of NASH. Key findings from the studies include:

• Improves Liver Injury in a Mouse Model of Cholestatic Liver Disease: A3907 improves liver injury and inflammation and decreases biliary hyperplasia and the characteristic sclerosing cholangitis of Mdr2-/- mice and is a promising new therapeutic tool for cholestatic liver diseases.
• Improves Key Clinical Markers of NASH in Obese Diet-Induced and Biopsy-Confirmed Mouse Models: In obese/obese-NASH and DIO-NASH mice, A3907 treatment improved key plasma and liver histological markers of NASH. Importantly, A3907 improved NALFD Activity Score and demonstrated no worsening in fibrosis stage. These findings introduce A3907 as a novel intervention for treatment of NASH and fibrotic progression.
• Data in both studies suggest that A3907 can be effective in cholestatic disease in addition to NASH.

About Bylvay (odevixibat)Bylvay is an investigational product candidate being developed to treat rare pediatric cholestatic liver diseases, including PFIC, biliary atresia and ALGS. A potent, once-daily, non-systemic ileal bile acid transport inhibitor (IBATi), Bylvay acts locally in the small intestine. Bylvay does not require refrigeration and can be taken as a capsule for older children, or opened and sprinkled onto food, which are factors of key importance for adherence in a pediatric patient population.

The FDA has granted Priority Review and set a PDUFA goal date of July 20, 2021. The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) recently issued a positive opinion recommending approval of Bylvay for the treatment of PFIC. Bylvay is the only IBATi granted accelerated assessment by the EMA. Bylvay also been granted Orphan Designation, as well as access to the PRIority MEdicines (PRIME) scheme for the treatment of PFIC. The EMA’s Pediatric Committee has agreed to Albireo’s Bylvay Pediatric Investigation Plans for PFIC and biliary atresia. In addition to PFIC, Bylvay has Orphan Drug Designations for the treatment of Alagille syndrome, biliary atresia and primary biliary cholangitis. With FDA and EMA regulatory submissions complete, Bylvay has the potential to become the first approved drug treatment for patients with PFIC in the U.S and Europe. The Company anticipates potential regulatory approvals, issuance of a rare pediatric disease priority review voucher and launch in the second half of 2021.

The MAA and NDA filings are supported by results from PEDFIC 1 and PEDFIC 2 Phase 3 studies. PEDFIC 1 was the first and largest, global, pivotal Phase 3 study conducted in PFIC, which evaluated the efficacy and tolerability of Bylvay in reducing pruritus and serum bile acids in a randomized, double-blind, placebo-controlled trial. In the PEDFIC 1 study, Bylvay met both primary endpoints and was well tolerated with very low incidence of diarrhea/frequent bowel movements (9.5% of Bylvay treated patients vs. 5.0% of placebo patients). ir.albireopharma.com/news-releases/news-release-details/albireo-phase-3-trial-meets-both-primary-endpoints-odevixibat. PEDFIC 2 is a long-term, open-label Phase 3 extension study. The Company also provides an Expanded Access Program (EAP) for eligible patients with PFIC in the U.S., Europe, Canada and Australia. Bylvay is also currently being evaluated in the BOLD Phase 3 trial in patients with biliary atresia, and the global Phase 3 ASSERT trial for ALGS.

About AlbireoAlbireo Pharma is a clinical-stage biopharmaceutical company focused on the development of novel bile acid modulators to treat rare pediatric and adult liver diseases. Albireo’s lead product candidate, Bylvay, is being developed to treat rare pediatric cholestatic liver diseases with Phase 3 trials in PFIC, Alagille syndrome and biliary atresia. For PFIC, the FDA recently granted Priority Review and set a PDUFA goal date of July 20, 2021. In Europe, the EMA’s CHMP recently issued a positive opinion and Bylvay is the only IBATi granted accelerated assessment by the EMA. Bylvay has been provisionally accepted by both the FDA and EMA as the brand name for odevixibat. The Company has also initiated 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 2020 Best Places to Work in Massachusetts for the second consecutive year. 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 or any other Albireo product candidate or program; expectations regarding the impact of the COVID-19 pandemic on our business and our ability to adapt our plans and activities as appropriate; the pivotal trial for Bylvay in biliary atresia (BOLD), and the pivotal trial for Bylvay in Alagille syndrome (ASSERT); 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, BOLD, ASSERT and the Phase 1 clinical trial for A3907; the potential approval and commercialization of Bylvay and the timing for such potential approval and commercialization; the potential for Bylvay to become the first approved drug for PFIC patients; discussions with the FDA or EMA regarding our programs; the potential benefits or competitive position of Bylvay or any other Albireo product candidate or program or the commercial opportunity in any target indication; the potential effects of Bylvay of the treatment of PFIC patients and its potential to improve the current standard of care; the potential benefits of an orphan drug designation; the potential issuance of a rare pediatric disease priority review voucher; or Albireo’s plans, expectations or future operations, financial position, revenues, costs or expenses. 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 the NDA for Bylvay for the treatment of pruritus in patients with PFIC will be approved by the FDA and whether the MAA for Bylvay in PFIC will be approved by the EMA; whether the FDA or EMA will complete their respective reviews within the target timelines, including the FDA’s PDUFA goal date, as a potential result of the impact of the COVID-19 pandemic or otherwise; the risk that the NDA will not be approved despite the FDA’s acceptance of the NDA for review or that the MAA will not be approved despite CHMP’s opinion recommending approval of Bylvay for the treatment of PFIC; whether the FDA or EMA will require additional information, whether we will be able to provide in a timely manner any additional information that the FDA or EMA requests, and whether such additional information will be satisfactory to the FDA and EMA; other potential negative impacts of the COVID-19 pandemic, including on manufacturing, supply, conduct or initiation of clinical trials, or other aspects of our business; 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; whether either or both of the FDA and EMA will determine that the primary endpoint for their respective evaluations and treatment duration of the double-blind Phase 3 trial in patients with PFIC are sufficient to support approval of Bylvay in the United States or the European Union, to treat PFIC, a symptom of PFIC, a specific PFIC subtype(s) or otherwise; the outcome and interpretation by regulatory authorities of the ongoing third-party study pooling and analyzing of long-term PFIC patient data; the timing for initiation or completion of, or for availability of data from, clinical trials of Bylvay or A3907, including BOLD and ASSERT, and the outcomes of such trials; Albireo’s ability to obtain coverage, pricing or reimbursement for approved products in the United States or European Union; delays or other challenges in the recruitment of patients for, or the conduct of, company’s clinical trials; and Albireo’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.comLisa Rivero, 617-947-0899, lisa.rivero@syneoshealth.com

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