GYS1

The investment is set to propel the development of the company’s lead candidates, MZE829 and MZE782. Credit: Mongkolchon Akesin/Shutterstock. Maze Therapeutics has completed a Series D financing round, raising $115m to propel the development of its lead candidates, MZE829 and MZE782. The financing round included the conversion of convertible notes previously acquired by existing investors. Deep Track Capital and Frazier Life Sciences co-led the financing round, with Logos Capital and Janus Henderson Investors also taking part. Existing investors include ARCH Venture Partners, Third Rock Ventures, GV, Matrix Capital Management, General Catalyst and Woodline Partners. An oral APOL1 inhibitor, MZE829 is under evaluation as a potential treatment for APOL1 kidney disease, including in individuals with focal segmental glomerulosclerosis. A Phase II trial is anticipated to commence by the first quarter of next year. Maze is also assessing the oral SCL6A19 inhibitor, MZE782, in a Phase I study involving healthy volunteers. The company has plans to further evaluate this candidate for the treatment of chronic kidney disease and phenylketonuria, with Phase I trial results expected in the second half of 2025. JP Morgan served as placement agent to Maze during the financing round. The company continues to advance its pipeline through its Compass platform, which leverages genetic insights to detect biological pathways linked to disease in certain patient groups. Maze Therapeutics CEO Jason Coloma stated: “We are grateful and honoured to have had the continued support of our long-term investors over the past several years and are thrilled to welcome the Frazier, Deep Track […] and Logos teams as we advance our two lead clinical programmes, MZE829 and MZE782, and continue to leverage our Compass platform. “The additional resources provided by this financing will allow us to optimise our upcoming Phase II trial of MZE829 and further explore the potential of both lead programmes. This financing marks an important step in our growth as a company, and for the patients we aim to serve.” In May 2023, the company entered an exclusive worldwide licence agreement with Sanofi for the glycogen synthase 1 (GYS1) programme and MZE001, an oral substrate reduction therapy, aimed at treating Pompe disease .

The second Trump administration is expected to focus on domestic M&A. Credit Brandon Bell / Getty Images. Trump’s return to the White House will mean a shift in personnel at the US Federal Trade Commission (FTC), which could mean more biopharmaceutical M&A deal activity in the country, an analyst has said. Considering the likely changes under the incoming Trump administration, GlobalData business fundamentals analyst Alison Labya commented: “A change in FTC leadership may encourage more M&A deals by large biopharmaceutical companies , as well as create a more favourable environment for smaller biotech companies to exit via acquisitions.” GlobalData is the parent company of Pharmaceutical Technology . The FTC’s role is to protect competition across US markets through the enforcement of antitrust laws. Trump is likely to replace its current chair Lina Khan, under whom M&A activity (in biopharmaceuticals and beyond) has seen increased scrutiny. FTC under Khan One pharmaceutical merger stopped by the FTC was Sanofi’s $750m licensing agreement with US-based biotech Maze Therapeutics, which has shared positive Phase I results for its glycogen synthase 1 inhibitor MZE001, an orally administered Pompe disease drug to be taken at home. Sanofi’s own Pompe treatment requires intravenous administration by a healthcare provider and costs around $750,000 for a year of treatment. In a statement , issued by Khan and Federal Trade Commissioner Rebecca Kelly Slaughter, the FTC claimed that Sanofi was “seek[ing] to buy out those competing treatments directly, eliminating the competitive pressure to innovate and offer more affordable drugs”. Following the FTC’s lawsuit, Sanofi terminated the licensing agreement and the complaint was dropped. However, Khan’s three years as FTC chair have earned her the reputation of being too tough. A report by the Committee of Oversight and Accountability published in October found that “Chair Khan seems committed to using all the FTC’s powers to throw sand into all the possible gears over proposed mergers, thereby halting many mergers by abuse of process and chilling other potential mergers from even being suggested”. FTC with a Trump pick Likely new agency leadership under Trump could well choose to unpick the Democrat-commissioner-approved 2023 guidelines, which reduced the Herfindahl-Hirschman Index (HHI) thresholds required for transactions to trigger a presumption of competitive harm. The FTC may therefore swing to a period of less rigorous antitrust scrutiny, at least in horizontal M&A. Regardless, businesses are preparing for a period of increased focus on domestic priorities. In his first term, Trump enacted the Foreign Investment Risk Review Modernization Act, which granted US regulators greater authority to review and block foreign M&A activity, both in biopharmaceuticals and beyond. Labya explained: “It remains uncertain whether Trump’s ‘America First’ foreign policies will pose challenges for companies outside of the US, especially those headquartered in China, looking to acquire US-based biopharmaceutical companies.” Trump has also made clear that he plans to impose heavy tariffs – “the most beautiful word in the dictionary”, he said – on imports. He has proposed a 60% tariff on goods from China and 20% on other countries. As a result, biopharmaceutical companies outside of the US may look to acquire US facilities to manufacture drugs domestically. However, Labya also warned that while some Trumpian policies may increase M&A activity, others risk deterring investors, quashing crucial biopharmaceutical innovation: “Furthermore, Trump’s plans to appoint Robert F Kennedy Jr – a known anti-vaccine advocate and critic of the FDA – as the head of the US Department of Health and Human Services may create challenges for future US drug approvals, which could dampen investor confidence and slow innovation in the biopharmaceutical industry.”

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