GYS1

Investigational, next-generation therapy for Pompe disease delivers GYS1 siRNA to muscle tissue Phase 1a safety and bioactivity data in normal healthy volunteers supports moving into first-in-patient LOPD trial PHILADELPHIA, PA, USA I October 29, 2024 I Aro Biotherapeutics , a clinical-stage biotechnology company working to develop potent and tissue-targeted medicines, today announced the initiation of the Phase 1b portion of its clinical trial of ABX1100, a novel potential treatment for late-onset Pompe disease (LOPD). By targeting a known receptor called CD71, ABX1100 delivers siRNA therapy to muscle tissue, where it inhibits the production of the GYS1 enzyme, which is responsible for synthesizing glycogen. In the planned 1b study, investigators seek to enroll adults with LOPD to evaluate the safety and bioactivity of ABX1100. More information about the trial is available at ClinicalTrials.gov using the identifier NCT06109948. “The limitations of enzyme replacement therapy for Pompe disease underscore the need for new therapies with novel mechanisms of action,” said Aneal Khan, MD, principal investigator of the trial and a pediatrician and medical geneticist at the Metabolic and Genetic in Calgary (MAGIC) Clinic in Alberta, Canada. “ABX1100 is being evaluated as a new therapeutic approach for individuals with late-onset Pompe disease, and we are eager to begin this trial in the underserved Pompe disease population.” Pompe disease is a rare neuromuscular disorder driven by the toxic buildup of glycogen, a stored form of sugar used for energy, in the muscle. This over-accumulation of glycogen leads to progressive loss of muscle function, weakness, and disability that can eventually progress to death from respiratory failure. 1 Currently available enzyme replacement therapies (ERTs) for Pompe disease have limited long-term efficacy. Preclinical studies suggest that inhibiting the production of GYS1 may be a valuable addition or alternative to ERT. “The encouraging preclinical and clinical evidence generated to date provides a solid foundation for ongoing clinical studies of ABX1100, which has the potential to be the first new treatment for Pompe disease beyond ERT. We anticipate dosing the first patient with Pompe disease in the Phase 1b study before the end of 2024,” noted Susan Dillon, Ph.D., co-founder, president and chief executive officer of Aro. “ABX1100 was well tolerated in a recently completed Phase 1a trial conducted in normal healthy volunteers, and it showed durable GYS1 mRNA knockdown in muscle biopsies, with effects lasting through at least 10 weeks following a single dose,” added Dr. Dillon. “The study achieved the goal of identifying a safe and effective starting dose for studies in patients with LOPD. We plan to present the Phase 1a results at a future medical conference.” About ABX1100 ABX1100, an investigational treatment for Pompe disease, is comprised of a CD71 receptor-binding Centyrin conjugated to a small interfering RNA (siRNA) that specifically interferes with expression of GYS1 messenger RNA (mRNA), thereby reducing levels and overall activity of the GYS1 enzyme in muscle tissues. ABX1100 demonstrated a favorable safety profile in toxicology studies, with durable reductions in GYS1 mRNA in muscles, supporting the potential for quarterly dosing. ABX1100 has received Orphan Drug Designation and Rare Pediatric Disease status from the United States Food and Drug Administration (FDA). About Aro Biotherapeutics Aro Biotherapeutics is a biotechnology company working to develop potent and versatile tissue-targeted genetic medicines with a platform based on a proprietary protein technology called Centyrins. The company is developing a wholly owned pipeline of Centyrin-based therapeutic candidates for tissue-specific targeting of therapeutics for a diverse set of diseases. For more information, visit www.arobiotx.com . Reference SOURCE : Aro Biotherapeutics

Eisai's bullish Leqembi sales projection, Takeda's Alzheimer's licensing deal and the latest on the BIOSECURE Act made our news this week. Following a reportedly bullish assessment from Medicare, Eisai has projected a significant sales increase for Leqembi. Takeda paid $100 million upfront for an option to license an anti-amyloid vaccine from AC Immune. The House Oversight Committee voted overwhelmingly to advance a tweaked version of the BIOSECURE Act. And more. 1. Eisai predicts sharp Leqembi sales increase as launch efforts begin to bear fruit After filing hitch, Eisai and Biogen begin rolling FDA submission for subcutaneous Leqembi Eisai expects Leqembi sales for its 2024 fiscal year will reach 56.5 billion Japanese yen ($364 million), compared with 4.26 billion Japanese yen ($27 million) during the 2023 fiscal year that ended in March. The company believes it and partner Biogen have improved Alzheimer’s disease diagnosis and treatment infrastructure in the U.S. and Japan. Meanwhile, after a short delay, the two companies have started a rolling FDA submission for a subcutaneous version of the anti-amyloid antibody that can be dosed at home. 2. Takeda pays AC Immune $100M upfront for Alzheimer's drug as phase 2 readout nears Fellow Japanese drugmaker Takeda is also making a bet on Alzheimer’s disease, paying $100 million upfront for AC Immune’s anti-amyloid beta vaccines. One candidate in the deal, coded ACI-24.060, is in a phase 1b/2 trial in patients with prodromal Alzheimer’s or Down syndrome. The option exercise fee and milestone payments could add up to $2.1 billion. 3. House's updated biosecurity bill sets 2032 decoupling deadline for industry's work with WuXi AppTec, WuXi Biologics In new letter to Defense Department, WuXi AppTec refutes claim of secret data transfer The House Committee on Oversight and Accountability voted overwhelmingly to advance the BIOSECURE Act for a full House vote, Reuters reports. The updated version of the bill would give biopharma companies until Jan. 1, 2032, to end their existing contracts with WuXi AppTec and WuXi Biologics plus three gene sequencing firms targeted in the legislation. For potential new targets of the bill, companies would have five years to cut ties with them. Meanwhile, WuXi AppTec is also defending itself against a claim that it shared a U.S. client’s data with Beijing without consent. 4. After FTC stalled Sanofi deal, Shionogi secures Maze's Pompe disease drug for $150M Five months after the U.S. Federal Trade Commission derailed Sanofi’s proposal to acquire Maze Therapeutics’ Pompe disease program, Shionogi has picked up the asset for $150 million upfront and undisclosed milestones. The candidate, MZE001, is a GYS1 inhibitor designed to stop the toxic buildup of glycogen. It has the potential to become the first oral treatment for Pompe. 5. Shionogi's antiviral comes up short in global COVID-19 trial Shionogi also suffered a setback this week. Its once daily protease inhibitor ensitrelvir, which is approved in Japan under the brand name Xocova, failed to significantly beat placebo in reducing the time to sustained resolution of 15 common COVID-19 symptoms in a global phase 3 trial. Despite the primary endpoint miss, Shionogi noted a significant difference in the time to resolution of six COVID symptoms. 6. Hengrui licenses GLP-1 portfolio to $400M biotech startup backed by Bain, Atlas (PDF, Chinese) A new GLP-1 player has emerged with $400 million funding from Bain Capital, RTW Investments, Atlas Venture and Lyra Capital plus a portfolio of three cardiometabolic candidates from Jiangsu Hengrui Pharma. Hengrui out-licensed the meds for $110 million in upfront and near-term payments, plus a 19.9% stake in the startup, called Hercules. One of the candidates is a dual GLP-1/GIP receptor agonist, the same mechanism as Eli Lilly’s tirzepatide. Other News of Note:  7. Under FDA scrutiny, Aurobindo's Eugia tallies a 5th Form 483 in less than a year 8. Radyus and Dt&CRO partner to bring more South Korean biotechs to the US

Shionogi CEO Isao Teshirogi, Ph.D., said Maze Therapeutics’ MZE001 is a “strong strategic fit” for his company. It appears Sanofi’s loss is Shionogi’s gain. Five months after the Federal Trade Commission (FTC) scuttled Sanofi’s attempt to acquire Maze Therapeutics’ Pompe disease program, Japan’s Shionogi has scooped up the asset. Maze and Sanofi unveiled their own licensing deal for the program, MZE001, back in May 2023. The French pharma agreed to pay $150 million upfront along with the potential for $605 million in milestones for worldwide rights to a drug candidate that could treat Pompe by stopping the buildup of glycogen. It looked like a good fit for Sanofi’s pipeline, where MZE001 would have sat alongside another Pompe treatment in the form of enzyme replacement therapy Nexviazyme. But the FTC saw that as a problem, arguing that the deal would “eliminate a nascent competitor poised to challenge Sanofi’s monopoly in the Pompe disease therapy market.” While Sanofi objected to the move, it didn't formally contest the agency's decision. By December 2023, the drugmaker had announced it was terminating the agreement. Step forward, Shionogi, which revealed this morning that it has acquired MZE001 for itself for the same upfront price tag of $150 million. While milestone payments are also attached to the deal, the precise amount wasn’t disclosed in the May 10 release. The upfront fee is in a different league to the 300 million Japanese yen ($1.9 million) Shionogi paid for its previous licensing deal in March—an anti-IgE antibody-induced peptide for seasonal allergic rhinitis developed by fellow Japanese biotech FunPep. Shionogi CEO Isao Teshirogi, Ph.D., said Maze’s MZE001 is a “strong strategic fit” for his company. “It will help meaningfully advance our commitment to develop innovative medicines that address unmet medical needs and complement Shionogi's rapidly expanding pipeline in the focus areas designated in our medium-term business plan,” Teshirogi added.  Shionogi pointed to the drug’s potential to become the first oral treatment for Pompe disease. If approved, the GYS1 inhibitor could be used both as a monotherapy or as an add-on therapy for enzyme replacement, which is the current standard of care for the condition, the company added. Paul Hudson may be another person who’s pleased to see MZE001 find a home. The Sanofi CEO has previously expressed concern that the failure to get their own licensing deal over the line put the drug’s future at risk. “Our first instincts on Pompe were, we’re just disappointed, that there’s a risk the program doesn’t continue,” Hudson said at the J.P. Morgan Healthcare Conference in January. “I just think sometimes capital is hard to come by; I think sometimes expertise isn't there, and I think sometimes in these smaller companies their desire was to get it to this point.”