Next-Generation Therapeutics Newsletter | June Roundup 2024

Highlights & Summary 

June was an exciting month for the next-generation therapeutics space, full of new clinical trial and regulatory updates.  

Happy reading!  

Cell Therapy 

1. FDA Eases Reporting Requirements for CAR-T Therapy Side Effects to Streamline Healthcare Processes | Regulatory 
2. Lyell Immunopharma Faces Safety Challenges in CAR-T Trial for Solid Tumors | Clinical Trial 
3. Kyverna Therapeutics' CAR T-Cell Therapy Shows Early Promise in Autoimmune Disease Trials | Clinical Trial 
4. Cabaletta Bio Reports Early Results from CAR T-Cell Therapy Trials in Autoimmune Diseases | Clinical Trial 
5. Kite Pharma Explores Cellares' Automated Manufacturing for CAR-T Therapies | Partnership 

Gene Therapy 

1. FDA Grants Sarepta Label Expansion for Elevidys | Regulatory  
2. Syncona Combines Freeline and Swan to Create Spur | M&A 
3. Astellas Initiates Research Collaboration with UMass for Alexander Disease | Partnership 
4. Fractyl Updates Timeline to Clinic for GLP-1 Gene Therapy | Clinical Trial  
5. Pfizer’s DMD Candidate Misses in Late-Stage Trial | Clinical Trial 

Oligo Therapy 

1. Roche and Ascidian Therapeutics Collaborate to Develop RNA Therapeutics Targeting Neurological Diseases | Partnership  
2. Silence Therapeutics’ Phase 2 Clinical Trial of Zerlasiran Shows Reduction in Lp(a) Relative to Placebo  | Clinical Trial  
3. Ethris Announces Positive Phase I Data for ETH47 Respiratory Indication Targeting Therapeutic | Clinical Trial
4. CSPC Myeloma Cell Targeting mRNA Therapeutic Obtains Approval for Clinical Trials | Clinical Trial  
5. Exsilio Therapeutics Secures $82M Series A Funding to Create Lipid-Nanoparticle Based mRNA Therapeutics | Financing 

Antibody-Drug Conjugates 

1. Blenrep Combination Reduced the Risk of Progression or Death in Multiple Myeloma | Clinical Trials 
2. Enhertu Demonstrated Clinical Benefit in HR positiveHER2low and Ultralow Breast Cancer | Clinical Trials 
3. BioNTech and DualityBio Receive FDA Fast Track Designation for BNT324/DB-1311 in Prostate Cancer | Regulatory 
4. Dyne Therapeutics Demonstrates the Potential to Deliver Enzyme Replacement Therapy in Pompe Disease | Pipeline 
5. Debiopharm and Genome & Company Reach Agreement for Potential First-In Class Oncology ADC Family | Partnership 

Cell Therapy 

FDA Eases Reporting Requirements for CAR-T Therapy Side Effects to Streamline Healthcare Processes | Regulatory 

The FDA has relaxed reporting requirements for two significant side effects—cytokine release syndrome (CRS) and neurologic toxicities—associated with certain CAR-T therapies, including Gilead’s Yescarta and Tecartus, and Bristol Myers Squibb’s Breyanzi and Abecma. This change, aimed at reducing the healthcare system's burden, follows extensive data collection and improved management of these side effects. Additionally, other requirements, such as educational materials for managing adverse reactions, have also been eliminated from the Risk Evaluation and Mitigation Strategies for these therapies. 

Lyell Immunopharma Faces Safety Challenges in CAR-T Trial for Solid Tumors | Clinical Trial 

Lyell Immunopharma's CAR-T therapy, LYL797, showed potential against solid tumors but raised safety concerns, including one patient's death due to respiratory failure. Of 16 evaluated patients, some experienced tumor shrinkage, but severe side effects like hypoxia and pneumonitis were observed, particularly in patients with metastatic breast cancer to lungs. The company plans to adjust dosing strategies. Lyell continues to explore CAR-T therapies for solid tumors, with ongoing developments in dosing and additional candidates targeting the ROR1 protein. 

Kyverna Therapeutics' CAR T-Cell Therapy Shows Early Promise in Autoimmune Disease Trials | Clinical Trial 

Kyverna Therapeutics' CAR T-cell therapy, KYV-101, has shown early promise in treating autoimmune diseases, achieving sustained remission in some patients. Tested in 30 patients across various conditions, the therapy has improved symptoms with mild side effects like cytokine release syndrome. KYV-101 targets CD19 on B cells to reset the immune system. However, lower dosing led to relapse in one patient. Kyverna continues to refine dosing and patient selection for future trials. 

Cabaletta Bio Reports Early Results from CAR T-Cell Therapy Trials in Autoimmune Diseases | Clinical Trial 

Cabaletta Bio has announced promising initial results from its Phase 1/2 trials using the CAR T-cell therapy, CABA-201, in treating autoimmune diseases. The therapy showed no serious adverse events. Early clinical data indicated improvements in disease measures for two patients, with complete B-cell depletion achieved by day 15 post-infusion. One patient demonstrated significant improvement in creatinine kinase levels and total improvement score. Both trials are part of Cabaletta's broader RESET clinical program, aiming to reset the immune system and achieve durable remission in autoimmune conditions without continuous medication. 

Kite Pharma Explores Cellares' Automated Manufacturing for CAR-T Therapies | Partnership 

Kite Pharma, a Gilead Sciences subsidiary, is exploring advanced manufacturing platforms for CAR-T therapies, including a new collaboration with Cellares to evaluate their automated Cell Shuttle platform. This evaluation follows Kite's recent partnership with Cytiva and aims to enhance their manufacturing capabilities. Cellares claims their platform reduces labor and facility requirements significantly compared to traditional methods, promising cost-effective production. The partnership could potentially replicate the success of Cellares' previous collaboration with Bristol Myers Squibb, which led to a significant manufacturing deal. 

Gene Therapy 

FDA Grants Sarepta Label Expansion for Elevidys | Regulatory  

Sarepta Therapeutics announced FDA approval for expanding the indication of ELEVIDYS (delandistrogene moxeparvovec-rokl) to include individuals with Duchenne muscular dystrophy (DMD) aged 4 and above with a confirmed DMD gene mutation. The FDA granted traditional approval for ambulatory patients and accelerated approval for non-ambulatory patients, contingent upon verification of clinical benefit in a confirmatory trial. ELEVIDYS is contraindicated in patients with deletions in exon 8 and/or exon 9 of the DMD gene. Sarepta will conduct a Phase 3 study to confirm clinical benefits for non-ambulatory patients. 

Syncona Combines Freeline and Swan to Create Spur | M&A 

Spur Therapeutics, formerly Freeline Therapeutics, announced a rebrand and its acquisition of SwanBio Therapeutics. The acquisition adds a gene therapy program for adrenomyeloneuropathy (AMN) to Spur's pipeline. Spur will initiate a Phase 3 trial for its Gaucher disease therapy FLT201 in 2025 and is advancing research on gene therapies for Parkinson’s disease and cardiovascular conditions. Syncona Ltd. has committed an additional $50 million to support these developments. 

Astellas Initiates Research Collaboration with UMass for Alexander Disease | Partnership 

Astellas Pharma US has partnered with UMass Chan Medical School to develop a gene therapy for Alexander disease, an ultra-rare and fatal CNS disorder. This one-year research agreement, with an option to extend, aims to accelerate clinical study efforts. Astellas will provide drug discovery expertise to support UMass Chan's research. This collaboration is the latest in a long list of investments Astellas has made across genetic medicines bolstering innovative R&D models. 

Fractyl Updates Timeline to Clinic for GLP-1 Gene Therapy | Clinical Trial 

Fractyl Health is developing a gene therapy aimed at transforming the pancreas into a GLP-1 drug producer, potentially removing the need for frequent injections like Ozempic. At the American Diabetes Association's conference, Fractyl presented data showing significant weight loss in mice treated with their therapy. Originally planning trials for 2024, the company now targets a clinical trial in diabetic patients in 2025, with future trials for obesity planned. While the therapy could provide a lasting weight loss solution, it raises questions about long-term side effects. Major companies like Novo Nordisk and Eli Lilly are exploring genetic medicines for weight loss but have not committed to similar gene therapies. 

Pfizer’s DMD Candidate Misses in Late-Stage Trial | Clinical Trial 

Pfizer announced that its Phase 3 CIFFREO study of the investigational gene therapy fordadistrogene movaparvovec in young boys with Duchenne muscular dystrophy (DMD) did not meet its primary endpoint of improved motor function. The study, which involved boys aged 4 to 7, showed no significant difference in motor function improvement compared to placebo, as measured by the North Star Ambulatory Assessment after one year. Secondary endpoints also did not show significant improvement. The company announced a patient death in a related trial testing the therapy in younger children last month. Pfizer plans to share detailed results at upcoming medical meetings and will continue monitoring participants while evaluating the program's next steps. 

Oligo   

Roche and Ascidian Therapeutics Collaborate to Develop RNA Therapeutics Targeting Neurological Diseases | Partnership 

Ascidian’s exon editing technology for neurological targets will be leveraged by Roche exclusively for preclinical activities, clinical development, manufacturing, and commercialization under a novel research collaboration and licensing agreement. Ascidian is set to receive an initial payment of $42M and potentially up to $1.8B in milestone payments for research and clinical objectives. As part of the agreement, Ascidian will grant Roche exclusive, target-specific rights to Ascidian's RNA exon editing approach for novel neurological targets.  

Silence Therapeutics’ Phase 2 Clinical Trial of Zerlasiran Shows Reduction in Lp(a) Relative to Placebo  | Clinical Trial 

Topline data from a Phase 2 Study of Zerlasiran shows a positive outcome of reduction of Lp(a) in treated patients for cardiovascular disease. The trial took place over 48 weeks in a double-blind, placebo-controlled procedure, where Zerlasiran was administered to patients subcutaneously. Median maximum Lp(a) reduction was observed at 90% or higher during the treatment period, and no adverse events were reported. The study is currently ongoing, with a report out at the 60-week mark. 

Ethris Announces Positive Phase I Data for ETH47 Respiratory Indication Targeting Therapeutic | Clinical Trial 

Ethris, a German biotechnology company has recently announced Phase I data showcasing safety of an intranasal mRNA therapeutic candidate ETH47, a type III interferon (IFN)-encoding mRNA. The drug is locally administered via a liquid nanoparticle-based delivery platform, and enters the lungs via inhalation. The data follows an announcement of $5M funding being secured for a Phase IIa study from the Bill and Melinda Gates Foundation.   

CSPC Myeloma Cell Targeting mRNA Therapeutic Obtains Approval for Clinical Trials | Clinical Trial  

A synthetic, mRNA- based cancer therapeutic developed by CSPC has received regulatory clearance to begin clinical testing in China. The drug, SYS6020 was developed for the targeting of myeloma cells and potential treatment of autoimmune disease. SYS6020 is currently the first mRNA-LNP-based cell therapy approved for clinical trials worldwide.  

Exsilio Therapeutics Secures $82M Series A Funding to Create Lipid-Nanoparticle Based mRNA Therapeutics | Financing  

Exsilio Therapeutics has announced emergence from stealth with $82M in funding secured for its Series A. Exsilio is currently backed by Novartis Venture Fund and Delos Capital, alongside OrbiMed, Insight Partners and J.P. Morgan Life Sciences Private Capital among others. Exsilio plans to use a platform combining in silico modeling and wet-lab based experimentation to integrate therapeutic genes in safe harbor sites, using mRNA-based approaches with lipid nanoparticle delivery mechanisms. 

ADCs  

Blenrep Combination Reduced the Risk of Progression or Death in Multiple Myeloma | Clinical Trials 

GSK announced that the combination of Blenrep with pomalidomide and dexamethasone significantly lowered the risk of disease progression or death by nearly 50% in patients with relapsed/refractory multiple myeloma compared to a standard treatment. Despite Blenrep's withdrawal from the US market in November 2022, the trial's results highlight its potential to improve outcomes and redefine treatment protocols for multiple myeloma patients, particularly those who have relapsed or are unresponsive to initial treatments. 

Enhertu Demonstrated Clinical Benefit in HR positiveHER2low and Ultralow Breast Cancer | Clinical Trials 

Enhertu has shown significant results in treating HR-positive, HER2-low, and HER2-ultralow metastatic breast cancer, demonstrating a median progression-free survival of 13.2 months. This marks a historic achievement as it is the first HER2-directed treatment to show substantial benefits for these patients. Data from DESTINY-Breast03 and DESTINY-Breast07 trials further reinforce Enhertu's role as a standard of care in second-line settings and highlight its potential in first-line treatments for HER2-positive metastatic breast cancer. This breakthrough has the potential to change the treatment landscape significantly. 

BioNTech and DualityBio Receive FDA Fast Track Designation for BNT324/DB-1311 in Prostate Cancer | Regulatory 

The two companies have received FDA Fast Track designation for their investigational ADC, BNT324/DB-1311, targeting advanced or metastatic castration-resistant prostate cancer. The decision is based on promising preclinical and Phase 1/2 trial data showing antitumor activity and a manageable safety profile. This marks the third ADC candidate in BioNTech and DualityBio's strategic partnership to receive Fast Track status, highlighting the strength and innovation of their ADC technology platform in oncology. 

Dyne Therapeutics Demonstrates the Potential to Deliver Enzyme Replacement Therapy in Pompe Disease | Pipeline 

Dyne Therapeutics unveiled preclinical data demonstrating their FORCE™ platform's capability to deliver enzyme replacement therapy (ERT) to muscle and the central nervous system for Pompe disease. This innovative approach shows potential for substantial improvement over current treatments, which primarily benefit cardiac and skeletal muscle but inadequately address CNS symptoms. This breakthrough could lead to a significant impact on the lives of patients with this severe neuromuscular disorder. 

Debiopharm and Genome & Company Reach Agreement for Potential First-In Class Oncology ADC Family | Partnership 

The two companies have entered into an exclusive licensing agreement to develop first-in-class ADCs. This collaboration grants Debiopharm global rights to develop ADCs that combine Genome & Company’s specific antibodies with Debiopharm’s proprietary Multilink™ technology. The agreement underscores the commitment of both companies to ADC innovation and leverages their strengths to collaborate on developing novel cancer treatments.