Intercept Pharmaceuticals, Inc.

Two of last years largest biotechnology company acquisitions centered on a new type of treatment for schizophrenia. By the end of September, the first of those therapies could win Food and Drug Administration approval, a decision that would highlight the new attention being paid to psychiatric drugs.Other novel psychiatric treatments are working their way through testing, too, including psychedelics like MDMA and psilocybin. The FDA has a tough decision to make on that front, as a panel of its advisers recently panned the use of MDMA-assisted psychotherapy for post-traumatic stress disorder.Elsewhere, Gilead Sciences might get an OK for a drug it recently acquired via its deal for CymaBay Therapeutics and a new kind of cell therapy could reach market. Here are five FDA decisions to watch in the third quarter:Bristol Myers Kar-XT for schizophreniaFor the first time in decades, a truly new form of antipsychotic could be coming to market.The drug, known as KarXT and developed by Karuna Therapeutics, already has multiple wins under its belt. Two large, placebo-controlled trials found schizophrenia patients given it had significantly greater reductions on a scoring system that measures the severity of their symptoms. The drug also seems to work fast, with the main treatment period of both studies lasting five weeks.While KarXT does have side effects, it doesnt appear to cause the excessive weight gain, restlessness or movement issues that older antipsychotics often elicit. Unlike those medications, KarXT and a rival medicine from Cerevel Therapeutics work by stimulating a kind of protein that controls the release of acetylcholine, a chemical important to brain function.Doctors foresee KarXT being an attractive option for schizophrenia patients, who often switch medications because of side effects or because the drugs arent controlling their disease well enough. Still, there are concerns that insurance providers will resist covering a drug like KarXT, since many generic and inexpensive antipsychotics are already available.On Wall Street, analysts expect KarXT will secure approval by the FDAs Sept. 26 decision deadline. Some even believe the drug will generate more than $10 billion in yearly sales at its peak. Whether that comes to fruition is in the hands of Bristol Myers Squibb, which recently bought Karuna for $14 billion.I think youre gonna get a massive bolus of early adopters, said Paul Matteis, an analyst at the investment firm Stifel, in an interview late last year. And I think Bristol [Myers] just has to not mess it up. Jacob BellLykos MDMA-based therapy for PTSDLykos Therapeutics believes it can build a business around MDMA also known as the party drug ecstasy. To do that, the company, formerly named MAPS Public Benefit Corp., identified a novel version of the drug and set up a series of patents to protect it.But Lykos needed supportive data as well. So far, it has run two late-stage studies evaluating MDMA as an aid to talk therapy for people with moderate-to-severe post-traumatic stress disorder. Results showed that, over the course of 18 weeks and three treatment sessions, patients who received MDMA had a significantly greater reduction on a scale measuring the severity of PTSD symptoms, compared to those who just got talk therapy.The company thought the trials provided enough evidence to make MDMA the first psychedelic-assisted therapy approved by the FDA. Those hopes appear slimmer, however, following a recent meeting of agency advisers.The panel of advisers voted almost unanimously against the drug, citing concerns about its safety and the ways Lykos conducted the trials. Allegations of ethics violations, including sexual misconduct and data suppression, also weighed on Lykos application.The FDA isnt required to follow the recommendations of its advisers. But it typically does, meaning the odds of approval are likely lower following the meeting. The agency is expected to make a decision by Aug. 11. Jacob BellGileads seladelpar for primary biliary cholangitisAfter spending more than $20 billion on cancer drug deals, Gilead got back to its liver disease roots with its February acquisition of CymaBay. The $4.3 billion buyout gave Gilead an experimental treatment for primary biliary cholangitis, a chronic condition caused by the toxic build-up of bile acid in the liver.Called seladelpar, the drug would expand Gileads liver disease portfolio beyond hepatitis if approved by the FDAs target decision date of Aug. 14. The company estimates about 130,000 people in the U.S. have primary biliary cholangitis, or PBC, and expects that its salesforce would cover about 80% of the prescribers who treat the condition.Two other drugs are approved in the U.S. for PBC: Intercept Pharmaceuticals Ocaliva and Ipsens more recently cleared Iqirvo. Both carry notable safety warnings, meaning that the labeling of seladelpar, if OKd by the FDA, could play an important role in how well its adopted. Testing of seladelpar in another liver condition called MASH was previously halted on safety worries that later proved unfounded.Gilead has highlighted seladelpars effectiveness in curbing the itching associated with PBC and expects the drug, if approved, to contribute modestly to sales this year. Ned PagliaruloAscendis TransCon PTH for hypoparathyroidismBy the end of the year, Takeda will stop making the only prescription medication available in the U.S. for a rare endocrine condition called hypoparathyroidism, ending a drug launch marred by slow sales and production issues. But a new option could emerge this quarter if the FDA approves TransCon PTH, a therapy developed by Danish biotech Ascendis Pharma.Ascendis drug provides a replacement form of parathyroid hormone, which is lacking in the estimated 77,000 people in the U.S. with hypoparathyroidism, causing low calcium levels and other health problems. Its based on a technology, TransCon, that Ascendis uses to fine-tune the properties of a medicine for delivery.Phase 3 study results in 2022 showed about 79% of trial participants treated with TransCon PTH had normal calcium levels. Most didnt need vitamin supplements afterwards. Ascendis has since won approvals in Europe and the U.K. But the company has faced a tougher road in the U.S. The FDA rejected TransCon PTH in 2023 due to manufacturing concerns and, in May, delayed its verdict by three months as the responses Ascendis provided constituted a major amendment to its application.A decision could finally come by Aug. 14 and, if positive, unlock what some analysts forecast as a multibillion-dollar revenue opportunity. An approval would also keep Ascendis ahead of several would-be competitors, among them AstraZeneca, which recently acquired a startup with a drug in late-stage testing. Ben FidlerAdaptimmunes afami-cel for synovial sarcomaSince 2017, the FDA has approved six CAR-T cell therapies and, earlier this year, cleared for the first time a different kind of immune cell treatment. Another type of cellular medicine could reach the market this quarter if the agency OKs an experimental drug from biotech Adaptimmune.Formed in 2008, Adaptimmune is focused on TCR cell therapies, which are similar to CAR-T treatments but rely on protein receptors that can recognize intracellular targets. That capability could make TCR cell therapies better able to attack the solid tumors CAR-T struggle to treat.But Adaptimmune has had difficulty proving their worth. In recent years, the company lost both GSK and Roche as partners, laid off staff and restructured its pipeline. At about $1 apiece, shares are worth a fraction of their initial public offering price in 2015.The companys fortunes could shift if the FDA approves afami-cel, a TCR therapy for a rare soft tissue cancer called synovial sarcoma. Wall Street analysts are optimistic the FDA will clear afami-cel by an Aug. 4 deadline, as the agency hasnt called on outside advisors to scrutinize the data or, executives have said, communicated issues with Adaptimunes study results. The company has financial room to work with, too, having cut deals with Galapagos and Hercules Capital in May.Still, Adaptimmune faces questions on afami-cels market potential. Analysts at Mizuho Securities have lowered peak annual sales projections to $174 million amid expectations of more conservative uptake than they previously thought. While an approval may bring validation to Adaptimmune, strong commercial performance will be important to support a positive view of the companys prospects, wrote Leerink Partners Thomas Chang in a recent client note. Ben Fidler '

Mr. Santini’s Extensive Global Commercial and Business Development Experience Strengthens Alzheon’s Board Leadership ALZ-801/Valiltramiprosate Has Potential to Become the First Oral Agent to Slow Alzheimer’s Pathology in Patients Fully Enrolled Pivotal APOLLOE4 Phase 3 Trial in Early Alzheimer’s Disease Patients on Track for Topline Data Readout and Initiation of NDA Submission in 2024 FRAMINGHAM, Mass.--(BUSINESS WIRE)-- Alzheon, Inc., a clinical-stage biopharmaceutical company developing a broad portfolio of product candidates and diagnostic assays for patients suffering from Alzheimer’s disease (AD) and other neurodegenerative disorders, today announced that it has appointed Gino Santini to its Board of Directors. "2024 is a transformational year at Alzheon and with the anticipated readout of our APOLLOE4 Phase 3 trial, we are preparing for potential approval and commercialization of our pathbreaking product. Gino’s addition to our Board of Directors will help guide this broadening of our focus from running clinical trials to executing regulatory submissions and planning for commercial launch in number of territories,” said Martin Tolar, MD, PhD, Founder, President, and CEO of Alzheon. “Alzheon’s well differentiated and simplified approach to disease modification has the potential to address crucial roadblocks in a market struggling to activate, and I look forward to strategic and business guidance from someone as experienced and accomplished as Gino.” Mr. Santini retired from a long and distinguished career at Eli Lilly in 2010. During his tenure at Eli Lilly, Mr. Santini held various leadership positions of increasing responsibility, including manager of various international regions, President of the Women’s Health Franchise and President of U.S. Operations. Mr. Santini capped his career at Eli Lilly as a member of the company’s executive committee and as Senior Vice President of Corporate Strategy and Business Development. Mr. Santini currently serves on the Boards of Directors of Intercept Pharmaceuticals and Collegium Pharmaceuticals. He previously served on the boards of SORIN SpA, Vitae Pharmaceuticals, Horizon Therapeutics, and AMAG Pharmaceuticals, until their acquisitions, and of Intarcia Therapeutics and Allena Pharmaceuticals. Mr. Santini is fluent in four languages and holds an undergraduate degree in mechanical engineering from the University of Bologna and an MBA from the University of Rochester. “Alzheon’s pioneering precision medicine and therapeutic approach has an opportunity to transform the standard of care and improve access to treatment for all Alzheimer’s patients, and it is an honor to be joining the Alzheon Board during this impactful period,” said Mr. Santini. “Bringing safe and effective therapies to the Alzheimer’s community is a noble mission and I could not be more excited about the prospects for Alzheon and the potential for ALZ-801 to fill a tremendous unmet medical need. APOLLOE4 Phase 3 trial evaluating oral ALZ-801 is expected to read out in the third quarter of 2024, and we are now preparing for a potential NDA submission this year followed by a commercial launch of the product in the U.S. in 2025.” About ALZ-801 ALZ-801/valiltramiprosate is a potential first-in-class, investigational oral agent in Phase 3 development as a potentially disease modifying treatment for AD.1,2,4,5 ALZ‑801 is designed to block the formation of neurotoxic soluble beta amyloid oligomers implicated in cognitive decline in Alzheimer’s patients.1,2,4 In mechanism of action studies, ALZ-801 has fully inhibited the formation of neurotoxic soluble beta amyloid oligomers at the Phase 3 clinical dose.6,7 ALZ‑801 acts through a novel enveloping molecular mechanism of action to block formation of neurotoxic soluble amyloid oligomers in the human brain8 associated with the onset and progression of cognitive decline in AD patients.1,2,4 ALZ-801 received Fast Track designation from the U.S. Food and Drug Administration in 2017 for Alzheimer’s disease. In clinical trials, ALZ-801 has shown potential for robust clinical efficacy and favorable safety results with no increased risk of brain vasogenic edema.6–8,10 The initial Phase 3 program for ALZ-801 is focusing on Early AD patients with two copies of the apolipoprotein ε4 allele (APOE4/4 homozygotes), with potential future program expansion to AD treatment and prevention in patients carrying one copy of the APOE4 gene and noncarriers.1–5 ALZ-801 Phase 2 Biomarker Trial Biomarker Effects of ALZ-801 in APOE4 Carriers With Early Alzheimer's Disease (NCT04693520): This ongoing trial was designed to evaluate the effects of 265 mg twice daily oral dose of ALZ-801 on biomarkers of AD pathology in subjects with Early AD, who have either the APOE4/4 or APOE3/4 genotype and constitute 65-70% of Alzheimer's patients. The trial also included evaluation of clinical efficacy, safety, tolerability, and pharmacokinetic pro ALZ-801 over 104 weeks of treatment. An ongoing long-term extension of the trial evaluates ALZ-801 for an additional 104 weeks of treatment for a total of 208 weeks. ALZ-801 APOLLOE4 Phase 3 Trial An Efficacy and Safety Study of ALZ-801 in APOE4/4 Early Alzheimer's Disease Subjects (NCT04770220): This ongoing trial is designed to evaluate the efficacy, safety, biomarker and imaging effects of 265 mg twice daily oral dose of ALZ-801 in Early AD subjects with two copies of the apolipoprotein ε4 allele (APOE4/4 homozygotes), who constitute approximately 15% of Alzheimer's patients. This is a double-blind, randomized trial comparing oral ALZ-801 to placebo treatment over 78 weeks. The APOLLOE4 trial is supported by a $51 million grant from the National Institute on Aging. An ongoing long-term extension of the trial evaluates ALZ-801 for an additional 52 weeks of treatment for a total of 130 weeks. About Alzheon Alzheon, Inc. is a clinical-stage biopharmaceutical company developing a broad portfolio of product candidates and diagnostic assays for patients suffering from Alzheimer’s disease and other neurodegenerative disorders. We are committed to developing innovative medicines by directly addressing the underlying pathology of neurodegeneration. Our lead Alzheimer’s clinical candidate, ALZ-801/valiltramiprosate, is a first-in-class oral agent in Phase 3 development as a potentially disease modifying treatment for AD. ALZ-801 is an oral small molecule that has been observed to fully block the formation of neurotoxic soluble amyloid oligomers in preclinical tests. Our clinical expertise and technology platform are focused on developing drug candidates and diagnostic assays using a precision medicine approach based on individual genetic and biomarker information to advance therapies with the greatest impact for patients. Alzheon Scientific Publications 1 Tolar M, et al: The Single Toxin Origin of Alzheimer’s Disease and Other Neurodegenerative Disorders Enables Targeted Approach to Treatment and Prevention, International Journal of Molecular Sciences, 2024; 25, 2727. 2 Tolar M, et al: Neurotoxic Soluble Amyloid Oligomers Drive Alzheimer’s Pathogenesis and Represent a Clinically Validated Target for Slowing Disease Progression, International Journal of Molecular Sciences, 2021; 22, 6355. 3 Abushakra S, et al: APOE ε4/ε4 Homozygotes with Early Alzheimer’s Disease Show Accelerated Hippocampal Atrophy and Cortical Thinning that Correlates with Cognitive Decline, Alzheimer’s & Dementia, 2020; 6: e12117. 4 Tolar M, et al: Aducanumab, Gantenerumab, BAN2401, and ALZ-801—the First Wave of Amyloid-Targeting Drugs for Alzheimer’s Disease with Potential for Near Term Approval, Alzheimer’s Research & Therapy, 2020; 12: 95. 5 Tolar M, et al: The Path Forward in Alzheimer’s Disease Therapeutics: Reevaluating the Amyloid Cascade Hypothesis, Alzheimer’s & Dementia, 2019; 1-8. 6 Hey JA, et al: Discovery and Identification of an Endogenous Metabolite of Tramiprosate and Its Prodrug ALZ-801 that Inhibits Beta Amyloid Oligomer Formation in the Human Brain, CNS Drugs, 2018; 32(9): 849-861. 7 Hey JA, et al: Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate in Development for the Treatment of Alzheimer’s Disease, Clinical Pharmacokinetics, 2018; 57(3): 315–333. 8 Abushakra S, et al: Clinical Effects of Tramiprosate in APOE4/4 Homozygous Patients with Mild Alzheimer’s Disease Suggest Disease Modification Potential, Journal of Prevention of Alzheimer’s Disease, 2017; 4(3): 149-156. 9 Kocis P, et al: Elucidating the Aβ42 Anti-Aggregation Mechanism of Action of Tramiprosate in Alzheimer’s Disease: Integrating Molecular Analytical Methods, Pharmacokinetic and Clinical Data, CNS Drugs, 2017; 31(6): 495-509. 10 Abushakra S, et al: Clinical Benefits of Tramiprosate in Alzheimer’s Disease Are Associated with Higher Number of APOE4 Alleles: The “APOE4 Gene-Dose Effect,” Journal of Prevention of Alzheimer’s Disease, 2016; 3(4): 219-228. View source version on businesswire.com: Contacts Source: Alzheon, Inc. View this news release online at:

Three years after Ispen licensed elafibranor from Genfit, it has gained FDA approval to treat the rare liver disorder primary biliary cholangitis (PBC). Once hyped as a potential blockbuster medicine for metabolic-associated steatohepatitis (MASH), Ipsen and Genfit’s elafibranor has found its calling as a treatment for a lower-profile liver disorder. The FDA has approved Iqirvo for primary biliary cholangitis (PBC), a chronic autoimmune condition which affects approximately 100,000 people in the U.S., most of them women between the ages of 30 and 60. PBC causes a buildup of bile and toxins, leading to inflammation and fibrosis of the liver. Over time, patients become increasingly fatigued and develop a debilitating itch (pruritis). In the absence of treatment, the condition can require a liver transplant or lead to premature death. Ipsen will charge $11,500 for a month’s supply of the first-in-class peroxisome proliferator-activated receptor (PPAR) agonist. After weak data eliminated elafibranor as a potential candidate for MASH, Ipsen in-licensed it from Genfit in 2021 as a treatment for PBC for 480 million euros ($515 million). The FDA endorsement is an accelerated nod, based on data showing that an 80 mg tablet of elafibranor reduces the rate of production of the alkaline phosphatase (ALP) enzyme—a key biomarker indicating the extent of liver damage. Achievement of a full approval will depend on success in confirmatory trials determining whether Iqirvo can improve survival and prevent abdominal swelling or gastrointestinal bleeding. The approval sets the two French companies up to compete with Intercept Pharmaceuticals’ Ocaliva, which has been on the market for eight years. Before Intercept was acquired by Italian private company Alfasigma last year, it expected sales of Ocaliva in 2023 to reach between $320 million and $340 million. Analysts estimate (PDF) sales of Iqirvo to reach 193 million euros ($207 million) in 2027. Peak sales have been tabbed at 400 million euros ($429 million). Alfasigma made its buyout of New Jersey-based Intercept shortly after the FDA rejected a bid for approval of Ocaliva in MASH for the second time in three years. Both Iqirvo and Ocaliva are approved for PBC in combination with ursodecxycholic acid (UDCA) or as a monotherapy in patients that can not take UDCA. Analysts at ODDO BHF said that the approval for Ipsen “marks a success story in the active business development policy since the appointment of current CEO David Loew in 2020,” and raises hopes for other partnerships. In regard to Iqirvo, however, one warning ODDO BHF had for investors is the lack of a reduction in pruritis on the label. The characteristic has “been seen as a weakness of Iqirvo,” the analysts wrote, especially in comparison to another drug expected to be approved in the indication in August—CymaBay Therapeutics’ seladelpar. In February of this year, Gilead gained the asset with a $4.3 billion buyout of CymaBay.