ADA

Researchers at the non-profit n-Lorem discovered and developed a personalised ASO therapy to treat a rare neurological disease. Credit: SurfsUp via Shutterstock. A patient with a rare progressive neurodegenerative disorder receiving a personalised experimental antisense oligonucleotide (ASO) treatment developed by the non-profit n-Lorem has reported improvements in seizure severity and quality of life. The patient, named Susannah, has a rare condition called KIF1A-associated neurological disorder (KAND). US-based non-profit n-Lorem developed a personalised, experimental ASO medicine specific to Susannah’s genetic mutation. After receiving her first dose of the personalised medicine, her seizures fell to under 30 per week and she has remained stable. KAND is caused by mutations in the KIF1A gene, leading to progressive motor impairments, developmental delays, and cognitive difficulties. Management of KAND mainly focuses on addressing symptoms and improving quality of life through supportive therapies, like speech or physical therapy. There are no other therapies for KAND in clinical development, as per GlobalData’s Pharma Intelligence Center. GlobalData is the parent company of Pharmaceutical Technology . Following the ASO treatment, the patient’s ability to walk also improved after one month; compared to having an average of 26.2 falls per day before treatment, she now experiences up to seven falls daily, with many days without any falls. See Also: Eli Lilly boosts sales forecast by $3bn as diabetes and weight loss drugs propel revenue Recursion and Exscientia merge to form drug discovery company Data from the study published in Nature Medicine also detail notable advancements in speech, attention, group interaction, and motor functions, while the patient’s cognitive abilities have remained stable. Susannah has continued on the ASO treatment for 20 months, with a favourable safety and tolerability profile. ASO therapies work by using short, synthetic strands of nucleic acids to target and modify specific genes, reducing the production of harmful proteins or correcting genetic defects. The treatment developed by n-Lorem targets and corrects the harmful version of the KIF1A gene. Founded by former Ionis Pharmaceuticals ’ CEO Stanley Crooke, n-Lorem aims to bring ASO therapies to patients who are diagnosed with a disease that is found in less than 30 people. Research physicians submit an application to the non-profit, which examines if the patient’s genetic mutation is amendable to the ASO technology. More than 130 patient applications have so far been approved by the organisation for a range of different mutations. There has been an increase in the number of nonprofits developing rare disease medications where the patient population size is too small for commercialisation. Italian research charity Telethon Foundation manufactures and distributes Strimvelis, a gene therapy for rare disease adenosine deaminase severe combined immunodeficiency (ADA-SCiD). The non-profit took over development after it was dropped by its pharmaceutical company in 2022, allowing patients to receive treatment. ASO therapies have long been investigated in rare diseases because they target the cause of disease at the molecular level. Researchers have also developed candidates that are approved to treat conditions affecting larger patient populations. Biogen ’s ASO Spinraza (nusinersen) secured approval for treating the movement disorder spinal muscular atrophy in 2016, pulling in $610.5m in sales in 2023 as per the company’s financials. In the announcement accompanying the case study, n-Lorem’s CEO Stanley Crooke said: “Prior to treatment, Susannah’s disease had progressed to her being mostly in a wheelchair, approaching nonverbal with debilitating seizures that limited her and her family’s quality of life. Susannah has now been on treatment for more than 20 months and we continue to observe improvements in her mobility, neurological function, and quality of life.” The non-profit, which launched in 2020, is also conducting a KIF1A outcome measures, assessments, longitudinal and endpoints (KOALA) study to understand how KAND symptoms develop and change over time.

Dive Brief:RNA editing startup Airna is adding more funds to its Series A round, raising another $60 million as it develops genetic medicines for lung, cardiovascular, metabolic and blood diseases.The Boston- and Germany-based biotechnology company made its debut last September with $30 million, launching with a plan to develop a medicine for the rare inherited disorder alpha-1 antitrypsin deficiency.Proceeds from the round will help the company take its AATD drug candidate into the clinic as early as next year, said Kris Elverum, Airnas CEO.Dive Insight:Airna describes its drugmaking approach as a safer alternative to the direct editing of DNA, such as via CRISPR-based techniques.“DNA is like the hardware of the cell, with the foundation,“ Elverum said. “RNA I think of as the software of the cell, which makes and operates the machines.“Airna was co-founded by Thorsten Stafforst, a professor studying RNA editing at the University of Tbingen, and by Jin Billy Li, a longtime geneticist and professor at Stanford University. The companys science is based around enzymes called adenosine deaminase acting on RNA, or ADAR, which help modify and regulate genes.The companys lead program is trying to correct the mutation that causes AATD, which can affect either the liver or lungs, and leads to conditions such as chronic obstructive pulmonary disease. Researchers estimate up to 100,000 people in the U.S. have the deficiency.Treatment of AATD depends on symptoms and can involve bronchodilators, antibiotics and, in some cases, injections of replacement AAT protein. A subcutaneous injection that is administered infrequently and “can repair the underlying disease“ would be preferable, Elverum said.RNA allows us to go after targets and root cause biology, but also have a drug product with a cost benefit that is quite favorable for large diseases and for treating earlier in the disease course, Elverum said.Airnas Series A extension was led by European life sciences investor Forbion, and also involved Arch Venture Partners, Ono Venture Investment, Alexandria Venture Investments and ND Capital. Its board of directors is chaired by Rodger Novak, the co-founder of CRISPR Therapeutics.A handful of companies are working on RNA-modulating treatments for AATD, including Wave Life Sciences, which launched a clinical trial for its drug this year. Among the drugs farthest along in clinical testing is Sanofi's INBRX-101, which it acquired in January as it was being tested in a Phase 2 trial, as well as Arrowhead Pharmaceuticals' experimental liver disease drug in development with Takeda. '

Nearly four years after it was spun out of George Church’s Harvard Medical School lab, GRO Biosciences is gearing up to bring its lead protein therapeutic into the clinic. The biotech clinched a $60.3-million series B on Friday to advance ProGly-Uricase into human testing for severe, refractory gout. The round, which brings GRObio’s total funding to $90 million, was co-led by new backers Atlas Venture and Access Biotechnology and saw participation from existing investors including Leaps by Bayer, Redmile Group, Digitalis Ventures and Innovation Endeavors. The firm had previously raised a $25-million series A in 2021.Aiming to “expand the amino acid alphabet,” GRObio uses its genomically recoded organism (GRO) platform to develop protein therapies based on non-standard amino acids (NSAAs) that enable the customisation of a therapeutic’s shape and chemical properties.Gout patients who don’t respond to front-line treatments are often given uricase enzyme therapy to break up the uric acid buildup that’s characteristic of the disease. According to the company, patients can develop anti-drug antibodies (ADAs) in response to treatment, “compromising safety and efficacy.”GRObio’s experimental drug was designed to avoid triggering an ADA response, as ProGly-Uricase is constructed with NSAAs that contain glycans. Those sugar molecules modulate the immune system to recognise the therapy as a “self” rather than foreign, preventing the launch of an immune attack.The company is also developing other ProGly-based therapies for autoimmune diseases that require the induction of highly specific tolerance to disease-causing autoantigens, without  broadly suppressing the immune system.