Next-Gen Therapeutics | April Round-Up
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Highlights & Summary
Intro
April was an exciting month for the next-generation therapeutics space, full of new clinical trial updates and manufacturing announcements.?
Happy reading!?
Cell Therapy
Antibody-Drug Conjugates
Gene Therapy
Oligo Therapy
Cell Therapy
BMS Announced Cost Saving Measures Including Cutting 2,200 Jobs, Affecting Its Cell Therapy Facility | Personnel
BMS, under CEO Chris Boerner, announced a substantial $1.5 billion cost-cutting strategy involving workforce reduction by 2,200, shutting down of its Redwood City cell therapy facility, and pipeline adjustments, amidst a stock dip. As part of the company's evolution and efficiency drive, the strategy will focus on high-potential R&D investments and smaller M&A activities, diverging from recent major acquisitions. With a shift in sales projections and anticipation of the Inflation Reduction Act's impact, BMS navigates through a strategic transition aiming for improved revenue growth in the coming years.
Enlivex Announces Phase 2 Sepsis Data That Proves Difficult to Read | Clinical Trial
Enlivex Therapeutics' cell therapy trial for sepsis yielded mixed results, with challenges in assessing its effectiveness due to pre-treatment patient conditions. However, the company noted a significant reduction in organ failure scores and mortality rates, especially in the urinary tract infection subgroup, suggesting a potential focus for future studies. Despite this, the unclear trial outcomes led to a steep drop in stock value. Enlivex, which previously halted its cancer programs to focus on inflammatory and autoimmune diseases, sees a considerable market in sepsis cases originating from UTIs.
Carisma Ends Clinical CAR-M Trials, Announces Lay-Offs | Clinical Trial
Carisma Therapeutics is halting two CAR-M cell therapy programs and reducing its workforce by 37% amid strategic refocusing. The company, which had 107 employees at the end of 2023, will lay off 39 staff members across R&D and corporate departments. Despite stable disease observed in a trial for its anti-HER2 CAR-macrophage therapy CT-0508, no new patients will be recruited. Carisma is shifting its efforts to CT-0525, an anti-HER2 CAR-monocyte therapy, with plans to start Phase 1 trials in Q2 this year. The company's partnership with Moderna continues, with a lead candidate nominated for in vivo CAR-M development. These changes are aimed at extending Carisma's operational runway into the third quarter of 2025.
Caribou Biosciences is venturing into the autoimmune disease sector, with FDA approval to start a lupus-focused clinical trial for its off-the-shelf CD-19-directed CAR-T cell therapy, CB-010, by late 2024. Already being tested for B cell non-Hodgkin lymphoma, Caribou plans a Phase 3 study in 2025, banking on the CRISPR-engineered PD-1 knockout for enhanced durability. CEO Rachel Haurwitz anticipates enrolling 20 patients across two cohorts, utilizing partial HLA matching to potentially improve outcomes without delaying treatment access. Updated data on the lymphoma study is expected soon, as Caribou positions itself in a crowded and competitive field.
BMS and Cellares Announce a $380M Global Agreement for the Manufacture of CAR-T Therapies | Manufacturing
Cellares has secured its first international contract with Bristol Myers Squibb, tapping into the momentum generated by the Biosecure Act, with increased interest from various potential clients. This $380 million deal reserves space for Bristol Myers' CAR-T therapies in Cellares' automated manufacturing facilities planned in the US, EU, and Japan. CEO Fabian Gerlinghaus highlights the strategic advantage of local manufacturing for CAR-T therapies, emphasizing that capacity is critical for capturing market share. With US facilities opening this year, Cellares aims to support Bristol Myers in meeting the growing demand for automated, end-to-end cell therapy production.
ADCs?
Corbus Doses First Patient with its Nectin-4 ADC | Clinical Trial
The company has initiated a Phase 1 for CRB-701, targeting Nectin-4, with the first patient dosed in the U.S. Preliminary data from a Phase 1 study in China suggests CRB-701 has a distinct pharmacokinetic and safety profile, potentially offering significant clinical benefits. The Nectin-4 ADC landscape is becoming increasingly competitive with over 15 ADCs in development.
The company has secured $132.5 million in Series C financing, led by AyurMaya, to advance its pipeline, including ENV-501, a novel HER3-targeted ADC for solid tumors. ENV-501 presents a differentiated approach with minimized off-target toxicity, positioning it uniquely in the landscape of HER3 ADCs for cancer treatment. There are currently over 20 anti-HER3 ADCs in development.
The FDA granted BVX001 Orphan Drug Designation for the treatment of AML. BVX001 is a CD3 and CD7 bi-specific ADC. BiVictrix currently has three disclosed ADCs in development for the treatment of both solid and hematological tumors.
Merck Acquires Abceutics | M&A
Abceutics, spun out of the University of Buffalo, has been acquired by Merck for $208 million. The company’s technology focuses on enhancing ADCs using payload-binding selectivity enhancers (PBSEs) to reduce side effects.
Enhertu Secures Tumor-Agnositc Indication Approval | Regulatory
In groundbreaking news, the FDA has granted Daiichi Sankyo US and AstraZeneca's Enhertu a tumor-agnostic indication approval under the accelerated pathway. This marks a significant milestone as it is the first approval of its kind for a HER2-directed therapy and the first ADC to receive a tumor-agnostic indication.
Gene Therapy
Pfizer Receives FDA Approval for Beqvez | Regulatory
Pfizer has received approval from the U.S. FDA for BEQVEZ? (fidanacogene elaparvovec-dzkt), a one-time treatment designed for adults with moderate to severe hemophilia B. BEQVEZ enables patients to produce factor IX themselves, offering an alternative to regular intravenous infusions of FIX. The therapy comes after CSL’s prior approval for their AAV product for the indication, Hemgenix. In parallel, Pfizer announced they are launching in parallel a warranty program for BEQVEZ to temper payer concerns. The company has set the list price at $3.5M/dose, tying Hemgenix as the world’s most expensive therapy.
AskBio’s Candidate Receives Fast-Track Designation | Regulatory
Bayer and AskBio have received Fast Track Designation from the FDA for their AB-1002 program, their gene therapy candidate for treating congestive heart failure. AB-1002 targets the production of a constitutively active form of protein inhibitor 1 to block the action of protein phosphatase 1, potentially leading to therapeutic effects on the heart. AskBio is currently enrolling patients in the Phase II GenePHIT trial to evaluate the safety and efficacy of AB-1002.
iECURE To Begin Gene Therapy Trial in Infants | Clinical Trial
iECURE, co-founded by UPenn Professor Jim Wilson, has received FDA approval to commence a clinical trial for their gene therapy targeting ornithine transcarbamylase deficiency in newborns and infants. This clinical trial will mark one of the first attempts to directly edit genes in infants to treat congenital diseases. While there are other programs in development for this indication from the likes of Ultragenyx, iECURE’s program is the first to target newborns and infants.?
Voyager and Neurocrine Advance GBA1 Candidate | Partnership
Voyager Therapeutics, in collaboration with Neurocrine Biosciences, has chosen a lead development candidate in their GBA1 gene therapy program for potential treatment of Parkinson’s disease and related conditions. The selection by the joint steering committee triggered a $3M milestone payment from Neurocrine to Voyager. The companies expect to file an Investigational New Drug application with the FDA for the program in 2025. The development candidate integrates a GBA1 gene replacement payload with a novel capsid derived from Voyager’s TRACER? capsid discovery platform.
Astellas’ Friedreich’s Ataxia Program to Enter Clinic | Clinical Trial
Astellas has received FDA clearance for its new gene therapy, ASP2016, aimed at treating Friedreich’s ataxia. This follows a setback with their previous candidate, AT808, which resulted in a $260 million writedown. ASP2016 targets the cardiac complications of Friedreich’s ataxia, utilizing a more mild promoter to ensure the therapy produces an optimal amount of frataxin protein without risking toxicity. The company anticipates dosing the first patient in the second half of 2024, marking Astellas' third gene therapy to enter human trials. The therapy received FDA Fast Track designation last month.
Oligo?
Moderna Announces Interim Data for Investigational mRNA Therapy | Clinical Trial
Interim data from Phase 1/2 trials of Moderna's investigational mRNA therapy, mRNA-3927, targeting propionic acidemia has been published, showing signs of potential clinical benefit. mRNA-3927 is an IV-administered, lipid nanoparticle therapy restoring PCC enzyme activity in the liver. The study demonstrated a relative reduction in risk of metabolic decompensation events by 70%, showing potential to reduce toxic metabolites and improve metabolic stability in patients.
Moderna Pauses Manufacturing Facility Development in Kenya | Manufacturing
Moderna’s efforts to build a manufacturing facility in Kenya have been paused, as demand for COVID-19 vaccines has declined since the pandemic. Since 2022, cancellation of vaccine orders for Africa have resulted in over $1B in losses and write-downs. Moderna is working on supporting public health vaccines for diseases predominantly affecting Africa, including HIV and malaria.
Phase 1 trial results were presented for an investigational mRNA vaccine (Autogene cevumeran (BNT122, RO7198457)) for treating pancreatic cancer developed through a collaboration between BioNTech and Genentech. The trial was led by MSKCC and the cancer vaccine candidate was shown to activate immune cells that persisted in the body up to three years after treatment in certain patients. Initial results from the Phase I trial were presented May 2023.?
Asahi Kasei and Axolabs will collaborate to build an oligonucleotide cGMP manufacturing facility in Berlin. This facility will leverage AKB’s suite of existing oligonucleotide manufacturing equipment to maximize productivity as Axolabs is a CRDMO providing drug substances for oligo-based therapeutics. The collaboration should facilitate the development and commercialization of oligo-based therapies.??
TriLink BioTechnologies and Lonza sign Licensing and Supply Deal for Streamlined mRNA Manufacturing | Manufacturing
TriLink BioTechnologies has signed a non-exclusive license and supply agreement with Lonza to supply its patented CleanCap AU cap analogs for usage in Lonza’s mRNA manufacturing and development services. The technology allows a one-pot solution with over 95% capping efficiency to streamline mRNA production processes. Since 2017, TriLink’s technology has been used in a majority of approved mRNA and saRNA vaccines. The latest CleanCap analog was introduced in May 2023, showing increased mRNA expression compared to enzymatic capping methods.