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Highlights & Summary
Intro
While we are closing out 2024, news in Next-Gen Therapeutics is still picking up, especially with regards to regulatory approvals across modalities.
Cell Therapy
- Gilead and Arcellx Present Promising Phase 1 Data for Their Multiple Myeloma Candidate | Clinical Trial
- Adaptimmunes’ Lete-cel Sarcoma Candidate Achieves Primary Endpoint in Pivotal Trial | Clinical Trial
Gene Therapy
- PTC Receives FDA Approval of KEBILIDI | Regulatory
- Genethon Announces Interim Clinical Data on DMD Prospect | Clinical Trial
Oligo Therapy
- Brii Bio Presents First Comparison of siRNA and PEG-IFNα Combination Therapy Against PEG-IFNα Alone | Clinical Trial
- Sarepta Therapeutics Enters Global Licensing Agreement with Arrowhead Pharmaceuticals for siRNA Programs | Partnership
- Vir Biotechnology Presents Positive Data from Chronic Hepatitis Delta Trial and Launches Phase 3 Program | Clinical Trial
- Silence Therapeutics Presents Phase 2 Zerlasiran Data | Clinical Trial
Antibody-Drug Conjugates
- Blenrep Shows Overall Survival Benefit in DREAMM-7 Phase III Trial for Relapsed/Refractory Multiple Myeloma | Clinical Trial
- Kelun-Biotech’s TROP2 ADC sac-TMT Receives NMPA Marketing Authorization in China for 2L+ Advanced TNBC | Regulatory
Cell Therapy
Roche to buy out Poseida for $1.5B Deal | M&A
Roche has entered into a definitive agreement to acquire Poseida Therapeutics, a clinical-stage biopharmaceutical company specializing in cell and gene therapies. The transaction includes an upfront payment of $9.00 per share, with an additional $4.00 per share (contingent upon achieving specific milestones). The brings the total potential value to approximately $1.5 billion. This acquisition aims to enhance Roche's capabilities in cell therapy, particularly in oncology, by integrating Poseida's platforms and current pipeline. The deal is expected to close in the first quarter of 2025.
FDA approves Autolus’ AUCATZYL for Adult R/R B-Cell ALL | Regulatory
Autolus Therapeutics has received FDA approval for AUCATZYL, a CAR T-cell therapy targeting CD19, designed to treat adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL). This approval is based on the FELIX clinical trial, which demonstrated a 63% overall complete remission rate among efficacy-evaluable patients. AUCATZYL is the first CAR T therapy approved by the FDA without requiring a Risk Evaluation Mitigation Strategy (REMS) program. Autolus plans to manufacture AUCATZYL at its dedicated commercial facility, the Nucleus, in Stevenage, UK.
Gilead and Arcellx Present Promising Phase 1 Data for Their Multiple Myeloma Candidate | Clinical Trial
Arcellx presented clinical data from its Phase 1 and iMMagine-1 studies on anitocabtagene autoleucel (anito-cel) in patients with relapsed or refractory multiple myeloma at the 66th American Society of Hematology (ASH) Annual Meeting. The Phase 1 study showed a median progression-free survival of 30.2 months, with a median follow-up of 38.1 months. Preliminary results from the iMMagine-1 Phase 2 study indicated a 95% overall response rate and a 62% complete response rate at a median follow-up of 10.3 months. No delayed neurotoxicities have been observed in over 140 patients treated across both studies. Additionally, the first patient has been dosed in the iMMagine-3 study, with manufacturing by Kite.
Adaptimmunes’ Lete-cel Sarcoma Candidate Achieves Primary Endpoint in Pivotal Trial | Clinical Trial
Adaptimmune's pivotal Phase 2 IGNYTE-ESO trial has met its primary endpoint, demonstrating a 42% response rate in patients with advanced or metastatic synovial sarcoma or myxoid/round cell liposarcoma (MRCLS). The trial included 64 participants who had previously undergone anthracycline-based therapy, with six achieving complete responses and twenty-one partial responses. Adaptimmune plans to initiate a rolling Biologics License Application (BLA) submission for lete-cel by the end of 2025, aiming to expand treatment options for patients with these challenging sarcoma subtypes.
FDA Approves StemCyte’s REGENECYTE for Unrelated Donor Transplants | Regulatory
The U.S. Food and Drug Administration (FDA) has approved StemCyte's Biologics License Application for REGENECYTE, a hematopoietic progenitor cell (HPC) cord blood product. This approval authorizes the use of REGENECYTE in unrelated donor hematopoietic progenitor cell transplantation procedures, in conjunction with an appropriate preparative regimen. The therapy aims to facilitate hematopoietic and immunologic reconstitution in patients with inherited or acquired disorders affecting the hematopoietic system, including those resulting from myeloablative treatment. StemCyte plans to collaborate with transplant centers nationwide to integrate REGENECYTE into clinical practice.
Gene Therapy
Novartis to Acquire Kate Therapeutics | M&A
Novartis has acquired Kate Therapeutics, a San Diego-based biotech company, to bolster its gene therapy pipeline for neuromuscular diseases, including Duchenne muscular dystrophy , facioscapulohumeral dystrophy , and myotonic dystrophy type 1. The deal, valued at up to $1.1 billion, includes Kate’s DELIVER platform, which develops muscle-targeted AAV gene therapies with improved tissue selectivity and reduced off-target effects. This acquisition aligns with Novartis' strategic focus on advancing innovative treatments for inherited neuromuscular disorders.
PTC Receives FDA Approval of KEBILIDI | Regulatory
PTC Therapeutics announced FDA accelerated approval of its gene therapy, KEBILIDI™ (eladocagene exuparvovec-tneq), for the treatment of aromatic L-amino acid decarboxylase (AADC) deficiency, marking the first U.S.-approved gene therapy directly administered to the brain. The therapy delivers a functioning DDC gene via a minimally invasive neurosurgical procedure to restore dopamine production, addressing a severe and life-shortening rare genetic disorder. Approval was based on clinical trial data showing motor function improvements, with long-term follow-up to confirm efficacy. PTC plans to launch KEBILIDI through centers of excellence. The therapy was previously approved in the EU and marketed as UPSTAZA.
Sangamo’s Neuropathy Candidate Receives IND Clearance | Regulatory
Sangamo Therapeutics announced FDA clearance of its investigational new drug application for ST-503, an epigenetic regulator designed to treat chronic, intractable pain caused by idiopathic small fiber neuropathy. ST-503 uses an AAV vector carrying a zinc finger repressor to target the SCN9A gene, reducing Nav1.7 sodium channel expression critical for pain signaling. Preclinical studies showed significant pain reduction and no off-target effects, supporting its potential as a one-time therapy. Sangamo plans to begin a Phase 1/2 trial in mid-2025, with future expansion to other chronic neuropathic pain conditions if successful.
Genethon Announces Interim Clinical Data on DMD Prospect | Clinical Trial
Genethon announced positive initial results from the Phase 1/2 portion of its ongoing Phase 1/2/3 trial of GNT0004, a gene therapy for Duchenne muscular dystrophy. The study showed patients experiencing stabilizatino or improvement in motor function compared to untreated patients from a natural history study at one to two years post treatment at higher doses. Based on these findings, Genethon plans to initiate a pivotal trial in Europe in mid-2025, followed by the U.S. The therapy utilizes an AAV8 vector and an optimized dystrophin gene delivered via a single intravenous injection.
CANbridge Publishes Dual-AAV Delivery Technology | R&D
CANbridge Pharmaceuticals announced the publication of a study in Science detailing the StitchR™ RNA assembly technology, which enables delivery of large genes, including full-length dystrophin, using dual AAV vectors. The technology allows seamless assembly of large gene sequences, producing a functional midi-dystrophin protein in preclinical models that is significantly larger than current micro-dystrophins used in approved therapies. This approach, forming the basis of CANbridge’s CAN204 DMD gene therapy program, showed improved muscle health in preclinical studies. CANbridge holds exclusive global rights to StitchR-enabled therapies targeting dystrophinopathies.
Oligo
Brii Bio Presents First Comparison of siRNA and PEG-IFNα Combination Therapy Against PEG-IFNα Alone | Clinical Trial
Brii Biosciences Limited presented new data from its ongoing Phase 2 ENSURE study at the AASLD Liver Meeting 2024. The study evaluated elebsiran, an investigational siRNA, in combination with PEG-IFNα for chronic HBV infection. Results showed significantly higher HBsAg seroclearance rates in the combination therapy groups compared to PEG-IFNα alone. The combination therapy demonstrated greater HBsAg reductions and was generally safe and well-tolerated.
Sarepta Therapeutics Enters Global Licensing Agreement with Arrowhead Pharmaceuticals for siRNA Programs | Partnership
Sarepta Therapeutics announced a global licensing and collaboration agreement with Arrowhead Pharmaceuticals, gaining exclusive rights to multiple clinical, preclinical, and discovery-stage programs for rare genetic diseases. The agreement covers four clinical-stage programs targeting various conditions, including facioscapulohumeral muscular dystrophy, myotonic dystrophy type 1, idiopathic pulmonary fibrosis, and spinocerebellar ataxia 2. Sarepta will also have access to Arrowhead's TRiM CNS delivery platform for three preclinical programs and a discovery collaboration for up to six additional targets. The collaboration aims to complement Sarepta's existing pipeline and expand its reach into new therapeutic areas, leveraging Arrowhead's siRNA technology.
Vir Biotechnology Presents Positive Data from Chronic Hepatitis Delta Trial and Launches Phase 3 Program | Clinical Trial
Vir Biotechnology presented positive results from the SOLSTICE Phase 2 clinical trial evaluating tobevibart alone or in combination with elebsiran for chronic hepatitis delta (CHD) treatment. The combination therapy achieved 100% virologic response and rapid hepatitis delta virus (HDV) RNA suppression, with 64% of participants reaching HDV RNA below the lower limit of quantification by Week 36. Based on these results, Vir Biotechnology plans to initiate the Phase 3 registrational ECLIPSE program in the first half of 2025. The safety profile of tobevibart and elebsiran was consistent with previous studies, with generally mild or moderate and transient treatment-emergent adverse events. The Phase 3 ECLIPSE program will include three randomized, controlled trials designed to evaluate the combination therapy in comparison to deferred treatment or bulevirtide in both cirrhotic and non-cirrhotic participants.
Silence Therapeutics Presents Phase 2 Zerlasiran Data | Clinical Trial
Silence Therapeutics presented end-of-treatment data from its Phase 2 ALPACAR-360 study of zerlasiran in ASCVD patients with high Lp(a) levels at the AHA Scientific Sessions 2024. Zerlasiran, administered at 300 mg every 16 or 24 weeks or 450 mg every 24 weeks, produced over 80% mean time-averaged placebo-adjusted reductions in Lp(a) concentrations over 36 weeks. Maximum Lp(a) reductions exceeded 90%, with persistent reductions observed at 60 weeks post-initial administration. The study reported time-averaged Lp(a) analyses for the first time, providing a more accurate evaluation of treatment effects over time. No safety concerns emerged with infrequent dosing of zerlasiran.
Codexis Achieves Enzymatic Synthesis of an Approved siRNA Therapeutic | Manufacturing
Codexis presented data at the TIDES Europe annual meeting demonstrating advancements in its Enzyme Catalyzed Oligonucleotide (ECO) Synthesis™ manufacturing platform for RNAi therapeutics. The company unveiled the first-ever end-to-end enzymatic synthesis of an approved siRNA therapeutic asset, inclisiran, including the enzymatic incorporation of a tissue-targeting moiety. Codexis' process operates under milder, aqueous conditions, improving product quality and reducing chemical waste compared to traditional phosphoramidite chemistry. The company also demonstrated superior performance of its engineered double-stranded RNA ligases over wild-type enzymes in synthesizing full-length siRNA therapeutic compounds, as validated through a joint poster with Bachem and customer case studies. Codexis plans to continue optimizing its process for robustness, scaled-up quantities, and improved purity, with the goal of providing customers with siRNA material of comparable or better quality to phosphoramidite chemistry.
ADCs
Alentis Therapeutics Raises $181M Series D Financing | Financing
Swiss biotech Alentis Therapeutics has raised $181M that will be used to launch clinical trials for its 2 ADCs. Novo Holdings, OrbiMed, and Jeito Capital have co-led the significant funding round. Alentis will use the money to advance a pipeline of medicines targeting Claudin-1 (CLDN1). More specifically, the new cash will be used towards launching a Phase 1/2 trial for ALE.P02, a potential first-in-class ADC carrying a tubulin inhibitor payload to treat advanced or metastatic solid tumors, and to move ALE.P03, a preclinical program targeting CLDN1+ tumors with a topoisomerase I inhibitor payload, into a Phase 1/2 trial sometime next year.
Lonza to Expand Bioconjugation with Two Additional Manufacturing Suites | Manufacturing
Lonza is expanding its Visp, Switzerland facility by adding two new multipurpose manufacturing suites, doubling its production capacity for antibody-drug conjugates (ADCs), and creating 200 new jobs. This expansion is set to go live by 2028 which will help enable Lonza to meet the growing demand for bioconjugates as ADCs and other bioconjugate drugs increasingly progress towards commercialization.
Entero Therapeutics Announces Reverse Merger with Journey Therapeutics | M&A
Entero Therapeutics is merging with Journey Therapeutics in a reverse merger, giving Journey 99% of Entero’s equity and rebranding under Journey’s name. The company will prioritize Journey’s nano-immunoconjugates (NIC) platform, a next-gen alternative to ADCs targeting hard-to-treat cancers and continue development of Entero’s phase 3-ready celiac disease candidate, latiglutenase. Journey CEO Henry Ji will lead the combined entity, which emerges as Entero navigates financial difficulties, including layoffs and debt restructuring.
Blenrep Shows Overall Survival Benefit in DREAMM-7 Phase III Trial for Relapsed/Refractory Multiple Myeloma | Clinical Trial
GSK’s multiple myeloma drug Blenrep has demonstrated a significant overall survival benefit over Johnson & Johnson’s Darzalex in the Phase 3 DREAMM-7 trial, bolstering its potential for $3.8 billion in peak sales. The antibody-drug conjugate showed a 59% reduction in progression or death risk and a strong survival advantage in combination with bortezomib and dexamethasone for previously treated multiple myeloma patients. This follows earlier setbacks, including Blenrep’s market withdrawal in 2022, but the drug is now poised for approvals in the U.S. and EU.
Kelun-Biotech’s TROP2 ADC sac-TMT Receives NMPA Marketing Authorization in China for 2L+ Advanced TNBC | Regulatory
Kelun-Biotech and Merck’s TROP2 ADC sacituzumab tirumotecan (sac-TMT) has received regulatory approval in China for treating advanced triple-negative breast cancer (TNBC) after two prior systemic therapies. This approval follows phase 3 results showing sac-TMT significantly reduced the risk of death and disease progression compared to chemotherapy. Sac-TMT, the first asset from Kelun and Merck’s ADC collaboration, is being further developed for earlier TNBC settings and EGFR-mutated non-small cell lung cancer (NSCLC).
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