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Highlights & Summary
Intro
August featured exciting developments across the next-gen therapeutics space, particularly for clinical trials in oligo therapies.
Cell Therapy
- Galapagos Halts Multiple Myeloma Trial Due to Neurological Concern, Expands Cancer Drug Partnership | Clinical Trial
- Cell Therapy Startup Avenge Bio Shuts Down, Lead Asset Returned to Rice University for New Company Launch | Commercial
- Legend Biotech Plans Major Carvykti Manufacturing Expansion to Meet Rising Demand in CAR-T Market | Manufacturing
Gene Therapy
- Lance Baldo in as CEO of Beacon Therapeutics | Personnel
- FDA Lifts Clinical Trial Hold on 4DMT’s Fabry Program | Clinical Trial
- BioMarin Deprioritizes Asset Licensed from DiNAQOR | Partnership
- Lacerta Therapeutics Shuts Down and Sells Assets | Company Creation
Oligo Therapy
- Arrowhead Pharma Advances Two RNAi-based Obesity Targeting Drugs into Clinical Studies | Clinical Trial
- Avidity Biosciences Announces Positive Results for Antibody-Oligonucleotide Conjugate Therapy for DMD | Clinical Trial
Antibody-Drug Conjugates
- Adcendo and Multitude Therapeutics Announce Global Development and Commercialization Agreement for First-in-Class ADC Drug | Partnership
- Aarvik Therapeutics Announces Option Exercise by Collaboration Partner ArriVent BioPharma | Partnership
- Angiex Announces First Patient Dosed in Phase 1 Clinical Trial for a Novel TM4SF1-Directed ADC | Clinical Trial
- Daiichi Sankyo and Merck Enter into Global Development and Commercialization Agreement for MK-6070 | Partnership
Cell Therapy
Galapagos Halts Multiple Myeloma Trial Due to Neurological Concern, Expands Cancer Drug Partnership | Clinical Trial
Galapagos has temporarily halted enrollment in its Phase 1/2 PAPILIO-1 trial for GLPG5301, a CAR-T therapy for relapsed and refractory multiple myeloma, after a patient developed Parkinsonism, a neurological issue. The company plans to adjust the trial protocol and resume recruitment in the coming months. GLPG5301, a BCMA-directed therapy, aims for faster treatment delivery compared to existing CAR-T therapies. Additionally, Galapagos expanded its partnership with BridGene Biosciences to develop a selective SMARCA2-targeting cancer drug, potentially earning BridGene up to $159 million plus royalties. Galapagos reported €3.4 billion in cash and investments as of June.
Cell Therapy Startup Avenge Bio Shuts Down, Lead Asset Returned to Rice University for New Company Launch | Commercial
Avenge Bio, a cell therapy startup, has shut down, ceasing all operations and returning its lead asset, AVB-001, to Rice University. The company had launched a Phase 1/2 trial for AVB-001, which was designed to treat peritoneal cancers like ovarian cancer by producing IL-2. Xontogeny, which co-led Avenge Bio’s $45 million Series A in 2022, confirmed the closure. AVB-001 is expected to be part of a new company launching soon.
Bluebird Bio Faces Financial Strain Amid Slow Uptake of Sickle Cell Therapy Lyfgenia | Commercial
Bluebird bio reported that only four patients have initiated the process for its sickle cell therapy, Lyfgenia, jeopardizing a $50 million loan crucial for its operations. The slow uptake led to renegotiated loan terms with Hercules Capital, requiring bluebird to secure additional financing by mid-December and meet patient start milestones by 2025. The company's financial difficulties highlight the challenges in commercializing gene therapies, with bluebird's stock falling 22% and its cash runway shortened to early 2025. Despite setbacks, bluebird continues to advance its other therapies, Zynteglo and Skysona.
Legend Biotech Plans Major Carvykti Manufacturing Expansion to Meet Rising Demand in CAR-T Market | Manufacturing
Legend Biotech plans to significantly increase Carvykti manufacturing as it competes with Bristol Myers Squibb and 2seventy bio in the CAR-T therapy market. CEO Ying Huang stated that patient demand for Carvykti is growing, and the company expects substantial sales growth in the latter half of the year as they expand production capacity. This includes anticipated approvals for their Ghent, Belgium facility and expansions at their Raritan, NJ site. Additionally, Novartis, a partner since April 2023, is set to begin commercial production of Carvykti in 2024. Carvykti outperformed its competitor Abecma in sales during the second quarter, highlighting the intense competition in the CAR-T space.
After the FDA released draft guidance on cell and gene therapy "platform" designations, companies like Regeneron, Alnylam, and Verve Therapeutics are asking for more clarity. While the guidance aims to expedite tech development, firms are unclear on its practical application, especially regarding multiple designations for the same product and confidentiality issues. Both industry and government agencies, including BIO and the Department of Defense, have requested more transparency and consistency in how the FDA will apply this new designation across different divisions.
Gene Therapy
Lance Baldo in as CEO of Beacon Therapeutics | Personnel
Beacon Therapeutics announced the appointment of Lance Baldo, MD, as Chief Executive Officer, effective August 12, 2024, and Thomas Biancardi as Chief Financial Officer, effective August 1, 2024. Baldo, a seasoned biopharmaceutical executive, succeeds David Fellows, who will transition to non-Executive Chairman of the Board in January 2025. These appointments follow Beacon's recent $170 million Series B fundraising. Beacon’s lead program, AGTC-501, is currently in a registrational trial for X-linked retinitis pigmentosa.
FDA Lifts Clinical Trial Hold on 4DMT’s Fabry Program | Clinical Trial
The FDA has lifted a clinical hold on 4D Molecular Therapeutics’ gene therapy for cardiomyopathy in Fabry disease, allowing the company to resume enrollment in its Phase 1/2 INGLAXA study of 4D-310 later this year. The trial had been paused in February 2023 after three patients experienced kidney issues, which were resolved within four weeks. 4DMT will initially focus on ex-US sites to confirm safety improvements. Jefferies analysts project potential U.S. approval by 2030 and peak global sales of $172 million by 2035.
Tome Biosciences to Layoff Team, Evaluate Strategic Options | Financing
Tome Biosciences is set to lay off nearly its entire workforce. The company, which launched publicly in December with $213 million in backing, was unable to secure additional funding needed to complete preclinical studies across their pipeline. CEO Rahul Kakkar confirmed that the company would shift its focus from lab work to finding an acquirer or partner to continue developing its gene editing technology. Tome had been developing a novel method for precise gene insertion leveraging multiple delivery vehicles, including combination AAV + LNP.
BioMarin Deprioritizes Asset Licensed from DiNAQOR | Partnership
BioMarin has decided to discontinue the development of BMN 293, a preclinical gene therapy for hypertrophic cardiomyopathy originally licensed from DiNAQOR AG, citing a strategic focus on assets with higher potential impact. Despite earlier preclinical data showing functional improvement in mice, the company has opted to shift resources away from BMN 293. This decision follows an April pipeline review, where BioMarin also dropped several other R&D programs. The company is now concentrating on three key candidates, including BMN 351 for Duchenne muscular dystrophy, BMN 349 for Alpha-1 antitrypsin deficiency, and BMN 333 for growth disorders.
Lacerta Therapeutics Shuts Down and Sells Assets | Company Creation
Lacerta Therapeutics has ceased operations and sold its assets, according to a board member. The company, a University of Florida spinout, faced challenges in securing funding amid a tough environment for early-stage gene therapy companies. Lacerta had partnerships with Sarepta Therapeutics, UCB, and Eli Lilly’s Prevail, but downsized last year and saw Sarepta terminate a license agreement in May 2023. Lacerta was developing gene therapies for conditions such as Pompe disease and Sanfilippo syndrome.
Oligo Therapy
First Participant Dosed in Clinical Trial for mRNA Cancer Vaccine for NSCLC | Clinical Trial
A BioNTech vaccine targeting non-small cell lung cancer (BNT116) has been administered to a patient in an early-stage clinical trial in the UK. The clinical trial is slated to take place across 34 research sites in seven countries in a global effort. The main objective of the study is to determine if BNT116 is safe and well-tolerated and will include patients at varying stages of NSCLC. Additionally, the trial will evaluate the safety of BNT116 as a monotherapy and in combination with existing treatments to identify any synergistic effects.
First Participant Dosed in Clinical Trial for siRNA-based Hypertension Drug | Clinical Trial
Innovent Biologics and SanegeneBio USA announced that the first participant has been dosed with a Phase 1, first in-human clinical trial of IBI3016, targeting angiotensin to treat hypertension. The trial will evaluate the safety profile of IBI3016, using single ascending doses in healthy patients and patients with mild hypertension. Preclinical studies have shown IBI3016 reduces serum AGT protein levels in monkeys, lowering blood pressure without inducing hypotension. Currently, Innovent Biologics maintains the exclusive option to license the manufacturing and commercialization of IBI3016, with IBI3016 having been developed using SanegeneBio’s proprietary siRNA platform.
Arrowhead Pharma Advances Two RNAi-based Obesity Targeting Drugs into Clinical Studies | Clinical Trial
Arrowhead Pharmaceuticals presented preclinical data to further pursue two RNAi-based therapeutic candidates (ARO-INHBE and ARO-ALK7) for the treatment of obesity and metabolic disease. Preclinical studies to date show the ability to reduce body weight and fat mass via a mechanism of action leading to improved muscle mass preservation. Specifically, ARO-INHBE targets the hepatic expression of the INHBE gene and its product Activin E, and ARO-ALK7 is design the suppress the adipose expression of ALK7, with both influencing the pathway regulating energy homeostasis in adipose tissue. Arrowhead will submit clinical trial applications with regulatory authorities for both treatments by the end of 2024, to begin in-human clinical trials in 2025.
Vion Biosciences Acquires Echelon to Target Customers in mRNA Biotherapeutics Delivery | M&A
VION Biosciences recently acquired Echelon, which supplies lipid-based excipients, to expand their product portfolio to include mRNA-based therapeutics and gene therapy manufacturing customers. The acquisition of Echelon builds on VION’s strengths in pre-clinical drug discovery, with Echelon’s team of lipidomics and mRNA drug delivery experts joining VION’s team. VION Biosciences is Iron Path Capital’s life science sector roll-up, and has already acquired Aldon, a chemical manufacturer, in 2023.
Avidity Biosciences Announces Positive Results for Orphan Drug-Designated, Antibody-Oligonucleotide Conjugate Therapy for DMD | Clinical Trial
Avidity Biosciences announced positive results for its AOC 1044 treatment (Del-zota) for Duchenne Muscular Dystrophy amenable to exon 44 skipping. Del-zota has previously demonstrated acceptable safety and tolerability profiles. The therapy showed a significant 25% increase in dystrophin production and showed reduced creatine kinase levels to near-normal ranges, indicating improved muscle function. Del-zota has been granted orphan designation by the FDA and EMA to fast track its commercial development.
Antibody-Drug Conjugates
Adcendo ApS and Multitude Therapeutics Inc. have signed a licensing agreement worth over $1 billion for the development of a novel antibody-drug conjugate (ADC) targeting tissue factor, a protein implicated in several cancers. This drug candidate leverages unique antibody design and linker-payload technology to improve therapeutic performance. The agreement highlights a significant investment in bringing this innovative treatment to market, leveraging Adcendo's clinical development expertise and Multitude's deep science strengths.
Aarvik Therapeutics Announces Option Exercise by Collaboration Partner ArriVent BioPharma | Partnership
Aarvik Therapeutics has announced that its collaboration partner, ArriVent BioPharma, Inc., has exercised the option to exclusively license a previous collaboration program. As part of an agreement dating back to December 2021, Aarvik has developed a novel antibody-drug conjugate (ADC) using its modular platform and is set to receive an upfront payment, research funding, and an opt-in payment, with potential for additional milestones and royalties in the range of $100M. ArriVent will now handle clinical development and commercialization efforts. Aarvik's advanced protein engineering and ADC expertise are recognized for enabling next-generation oncology therapies, and the milestone highlights the efficacy of their multi-targeting platforms in addressing difficult cancer indications.
GSK Receives U.S. FDA Breakthrough Therapy Designation for its ADC in ES-SCLC | Regulatory
GSK has received Breakthrough Therapy Designation from the US FDA for its investigational B7-H3-targeted antibody-drug conjugate, GSK5764227 (GSK’227), aimed at treating relapsed or refractory extensive-stage small-cell lung cancer (ES-SCLC). This designation accelerates the development and review process for drugs showing potential to significantly improve treatment outcomes for serious conditions. GSK’227, which is in early clinical trials showing promising results, will benefit from expedited review to address the urgent need for better therapies in this aggressive cancer type. GSK plans to initiate global Phase 1/2 trials later in 2024 to support the drug’s regulatory approval.
Angiex Announces First Patient Dosed in Phase 1 Clinical Trial for a Novel TM4SF1-Directed ADC | Clinical Trial
Angiex Inc. has initiated a Phase 1 clinical trial for AGX101, a novel TM4SF1-directed antibody-drug conjugate (ADC) designed to treat solid tumors. AGX101 targets TM4SF1, which is present in both tumor cells and tumor vasculature and employs a unique internalization pathway for delivering chemotherapy directly to the nucleus of cancer cells. The trial aims to evaluate the safety, pharmacokinetics, and preliminary anti-tumor activity of AGX101. Angiex, known for its Nuclear-Delivered Antibody-Drug Conjugates™ (ND-ADCs), is optimistic about AGX101’s potential as a first-in-class drug to address high unmet needs in cancer treatment.
Daiichi Sankyo and Merck Enter into Global Development and Commercialization Agreement for MK-6070 | Partnership
Following a $4 billion deal with Daiichi Sankyo last year, Merck is recouping some investment as Daiichi buys into a Phase I/II T-cell engager therapy acquired from Harpoon Therapeutics. The expanded partnership will see Daiichi invest $170 million to co-develop Merck’s investigational T-cell engager, MK-6070, targeting DLL3 in small cell lung cancer and neuroendocrine tumors, while Merck retains rights in Japan. MK-6070, a key asset from Merck’s $680 million Harpoon acquisition earlier this year, and is already in trials, and will be synergized with the companies' established antibody-drug conjugate collaboration. This collaboration also follows Amgen’s recent approval of a similar DLL3-targeting T-cell engager.
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