News Briefing: 10/16 - 10/24
10/16 – Wave Achieves First-Ever RNA Editing in Human
Wave Life Sciences announced positive proof-of-mechanism data from its ongoing phase 1a/2a study of GalNAc-conjugated RNA editing oligonucleotide (called WVE-006) in treating alpha-1 antitrypsin deficiency (AATD).1 The oligonucleotide recruits the Adenosine deaminases acting on RNA (ADAR) to correct a single-base mutation in AAT mRNA (A-to-I). The misfolded mutated AAT protein gets trapped in the liver and decreased levels of circulating wild-type AAT fails to defends the lungs against enzymes like neutrophil elastase that break down tissue, causing liver and lung diseases.2 The data Wave released show that a single subcutaneous dose of WVE-006 in the first two patients with homozygous “ZZ” AATD who are unable to naturally produce wild-type M-AAT, resulted in mean plasma total AAT levels of ~11 micromolar with mean M-AAT accounting for more than 60% of total AAT. The increase lasted until Day 57. Multidose data from the trial is expected in 2025. After successful completion of the trial, Wave is eligible for a lump sum payment and tiered royalties on net sales from their GSK collaborator, who is responsible for further development and commercialization.
Reference:
2. https://ir.wavelifesciences.com/static-files/d233d4aa-f7ee-4beb-b6f4-92234e1a756e
10/17 – Merck’s RSV Antibody Enter Race with AZ and Sanofi’s Beyfortus
Merck presented positive results from the Phase 2b/3 trial of clesrovimab, the prophylactic mAb for prevention of respiratory syncytial virus (RSV) in infants from birth to one year of age. The results show that a single-dose shot for healthy and at-risk infants regardless of weight met all prespecified endpoints.1 Clesrovimab reduces the incidence of RSV-associated medically attended lower respiratory infections (MALRI) by 60% compared to placebo through the first five months after dosing. It also reduces RSV-associated hospitalizations and RSV-associated LRI hospitalizations compared to placebo by 84.2% and 90.9%, respectively. Interim data from a Phase 3 trial showed comparable safety of clesrovimab to Synagis, an antibody drug only for high-risk infants approved in 1998. Merck is aiming for entering the RSV market for infants as early as the 2025-36 season. They will be up against the only other preventive RSV drug for infants Beyfortus from Sanofi and AZ that showed a 74.9% reduction of RSV-associated MALRI compared to placebo with different dosings depending on infant weights. Beyfortus was approved in 20232 and garnered $592 million in sales in 2023. Adult RSV vaccines include Pfizer’s Abrysvo for pregnant women, GSK’s Arexvy and Moderna’s mResvia (approved May, 2024).
Reference:
1. https://www.businesswire.com/news/home/20241017875997/en
10/21 – Seaport Therapeutics Raised $225 Million in Series B Funds
Seaport Therapeutics, successor to Karuna Therapeutics with antipsychotic drug KarXT acquired by BMS in a $14 billion deal, has welcomed fundings from Biotech investors like Arch Venture Partners, Sofinnova Investments, Third Rock Ventures and PureTech Health, who also invested in Series A.1 Seaport’s central program lies with its Glyph platform2 that links the active ingredients to triglyceride mimetic fatty acid through a proprietary linker to promote lymphatic transport to bypass the liver and increase oral bioavailability. Its lead candidate, SPT-300, is leveraging on the company’s platform to overcome the challenge of low bioavailability of allopregnanolone as an oral pill for treating postpartum depression, which is the active ingredient of the branded IV infusion drug Zulresso by Sage Therapeutics.
Reference:
2. https://seaporttx.com/our-pipeline/
3. https://doi.org/10.1016/j.jconrel.2021.02.008
10/22 – Otsuka’s IgAN Drug Hits Phase 3 Trial Primary Endpoint
Otsuka’s IgAN drug sibeprenlimab acquired from Visterra has met its Phase 3 trial primary endpoint in reducing the patients’ urine protein-to-creatine ratio (UPCR) levels in a statistically significant and clinically meaningful way. Sibeprenlimab targets the A proliferation-inducing ligand (APRIL) to limit the production of Gd-IgA1, the build-up of which would cause IgAN, thus stalling progression of the disease. Although with a differentiated mechanism, the drug is entering a space with growing competitors reducing the immune-mediated drivers like Novartis’ Fabhalta (a complement inhibitor), Calliditas’ Tarpeyo (a B-cell immunomodulator) and Travere’s Filspari (dual endothelin angiotensin receptor antagonist (DEARA)). Vertex acquired Alpine Immune Sciences and gained access to povetacicept (dual inhibitor to APRIL and BAFF). Biogen acquired HI-Bio and gained access to Felzartamab (CD38 inhibitor).
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10/22 – Editas to Partner or Out-License Reni-Cel to Pivot to In-Vivo Gene Editing
Editas has initiated process to find opportunities for partnering or out-licensing its ex vivo hemoglobinopathies reni-cel to focus on developing in vivo therapy following achievement of preclinical proof-of-concept results.1 Editas reni-cel therapy for treating severe sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT) are in clinical trials and have been shown to work as durable one-time medicine.2 Editas is claiming it as future “best-in-class” therapy compared to already approved therapies like Vertex’s Casgevy and bluebird bio’s Lyfgenia. In moving forward, the company is focusing its financial resources on in vivo pipeline. They report positive preclinical in vivo hematopoietic stem and progenitor cell (HSPC) editing results. The announcement reports a 29% editing after a single dose by targeted lipid nanoparticle (LNP) extrahepatic tissue delivery in a humanized mouse model and HbF induction as shown by a mean 20% HbF expression on human red blood cells by one month.1 Editas is developing its LNP expertise both in house and through collaboration. It is looking to collaborate with a nucleic acid delivery company, Genevant Sciences, to develop Cas12a-based in vivo gene editing medicines for two undisclosed targets.3
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10/24 – Septerna Goes Public with $288 Million IPO
The G protein-couple receptors (GPCRs) company is pricing its IPO at $288 million,1 reflecting strong investor interest in its GPCR isolation platform and lead candidate SEP-786. The drug is an oral small molecule parathyroid hormone (PTH) 1 receptor (PTH1R) agonist for treating hypoparathyroidism characterized by low levels of PTH caused by the loss of parathyroid glands. This drug could offer a simple oral alternative to the current treatments of life-long daily injections and calcium supplements. Several GPCR-related biotech has gone to IPO recently including Structure Therapeutics (raised $161 million),3 Escient Pharmaceuticals (acquired by Incyte)4 and Tectonic Therapeutic (reverse merger).5
Reference:
1. https://www.nasdaq.com/events/septerna-rings-opening-bell
