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Highlights & Summary

Intro

December was an exciting month for the next-generation therapeutics field, full of new partnerships formed and clinical trial updates announced. 

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Cell Therapy

1. Shinobi Therapeutics Launches with Completion of $51M Series A to Advance Hypoimmune iPS-T Cell Therapy Platform | Financing

2. Autolus Therapeutics Presents Clinical Data Updates at the ASH Annual Meeting 2023 | Clinical Trials

3. Poseida Therapeutics Presents Early Results from its Phase 1 Trial of Allogeneic CAR-T P-BCMA-ALLO1 in Multiple Myeloma at the ASH Annual Meeting 2023 | Clinical Trials

4. Clinical Holds Impact CARsgen Therapeutics' Three CAR-T Programs Following FDA Manufacturing Concerns | Regulatory

5. Cellectis Boosts CAR-T Therapy Efficacy with In-House Manufacturing, Showcases Improved Trial Results | Manufacturing

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Antibody-Drug Conjugates

1. SystImmune and BMS Announce a Strategic Collaboration | Partnership

2. C4 Therapeutics Announces a Collaboration with Merck | Partnership

3. Avidity Biosciences Reports Positive Data for AOC 1044 in DMD | Clinical Trial

4. Nano Biosciences Enters an Agreement with Pfizer | Partnership

5. Sanofi Ends the Development of Its Only Clinical ADC | Clinical Trial

6. LegoChem and Janssen Enter a License Agreement | Partnership

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Gene Therapy

1. Atsena Releases Positive Results from PhI/II for LCA1 Candidate | Clinical Trial

2. uniQure Provides Another Look at Huntington’s Candidate | Clinical Trial

3. MeiraGTx Sells Rights to AAV5-RPGR to J&J for up to $415M | Partnership

4. Takeda Ends Partnership with JCR as Former Deprioritizes AAV | Partnership

5. 4DMT Receives RMAT Designation from FDA for Wet AMD Candidate | Regulatory

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Oligo Therapy

1. SanegeneBio and Innovent Enter Partner to Develop Hypertension siRNA Therapies | Partnership

2. A First-in-Class Inhaled mRNA for Respiratory Viral Infections Enters Phase 1 Study | Clinical Trial

3. Moderna Publishes Pivotal Phase 3 Clinical Data on Investigational RSV Vaccine, MRNA-1345, in New England Journal of Medicine | Clinical Trial

4. Arrowhead Pharmaceuticals Seeks Regulatory Approval to Commence Phase 1/2a Trial of ARO-CFB in Complement-Mediated Kidney Disease | Clinical Trial 

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Cell Therapy

Shinobi Therapeutics Launches with Completion of $51M Series A to Advance Hypoimmune iPS-T Cell Therapy Platform | Financing

Shinobi Therapeutics, a biotech formed from a merger between Japanese and Bay Area startups, has raised $51 million in Series A funding. The company, focused on developing off-the-shelf cell therapies for cancer and autoimmune diseases, plans to begin Phase I trials in Japan in 2025 and expand to the U.S. for Phase II. Shinobi's approach, backed by research from Kyoto University and UCSF, aims to create cell therapies that eliminate the need for immunosuppressive drugs. The company is led by CEO Dan Kemp and has attracted notable figures like CAR-T pioneer Carl June to its scientific advisory board.

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Autolus Therapeutics Presents Clinical Data Updates at the ASH Annual Meeting 2023 | Clinical Trial

Autolus is developing obe-cel, a CD19-directed CAR-T therapy for relapsed/refractory adult acute lymphoblastic leukemia, targeting the same indication as Gilead’s Tecartus. Recent pooled analysis of 127 patients showed a 78% complete response rate, with promising event-free survival statistics. With an FDA application submitted in late November, Autolus anticipates a 2024 decision. If approved, obe-cel will directly compete with Tecartus. Autolus, reporting a strong cash position, may seek additional capital for launch through collaborations. The company highlights obe-cel's safety profile, showing lower rates of severe cytokine release syndrome compared to Tecartus, potentially offering a safer alternative.

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Poseida Therapeutics Presents Early Results from its Phase 1 Trial of Allogeneic CAR-T P-BCMA-ALLO1 in Multiple Myeloma at the ASH Annual Meeting 2023 | Clinical Trials

Poseida Therapeutics showcased early data for its Roche-partnered allogeneic CAR-T therapy, P-BCMA-ALLO1, indicating promising results. The Phase 1 trial data, presented at the American Society of Hematology Annual Meeting, revealed an 82% ORR in patients who received higher cyclophosphamide doses and no severe adverse events reported. Poseida and Roche are continuing the Phase 1 trial, exploring different dosing and conditioning regimens, with more data expected next year. The trial's success could be significant given the FDA's ongoing safety review of CAR-T therapies and their associated risk of secondary cancers.

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Clinical Holds Impact CARsgen Therapeutics' Three CAR-T Programs Following FDA Manufacturing Concerns | Regulatory

CARsgen Therapeutics faces clinical holds on three of its CAR-T therapies (CT053, CT041, and CT071) due to concerns related to chemistry, manufacturing, and controls, following an FDA inspection of its Durham, NC manufacturing site. The hold affects trials targeting BCMA, Claudin18.2, and GPRC5D, with CT041 also being explored in combination with Moderna’s mRNA cancer vaccine in preclinical stages. The company's shares dropped about 30% following the news. Despite this setback in the U.S., CARsgen continues separate studies in China, including positive three-year follow-up results for CT053 in Chinese patients. 

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Cellectis Boosts CAR-T Therapy Efficacy with In-House Manufacturing, Showcases Improved Trial Results | Manufacturing

Cellectis, a CAR-T biotech, transitioned its manufacturing in-house due to inefficiencies with third-party producers, enhancing its production and therapy efficacy. This strategic move, which included producing their own raw materials, led to better results in their Phase I BALLI-01 trial for UCART22. Despite the substantial investment required for in-house manufacturing, Cellectis has improved control over its processes but does not plan to provide manufacturing services to other companies.

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ADCs 

SystImmune and BMS Announce a Strategic Collaboration | Partnership

The two companies have entered into an exclusive $8.4 billion license and collaboration agreement for the development of BL-B01D1, a promising bispecific ADC designed for the treatment of solid tumors, with a particular emphasis on lung and breast cancer. Currently undergoing evaluation in a global Phase I study, BL-B01D1 has exhibited significant antitumor activity in various solid tumors during earlier clinical studies. This collaboration is in line with BMS's strategic focus on diversifying its oncology portfolio and expanding therapeutic modalities across solid tumor oncology.

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C4 Therapeutics Announces a Collaboration with Merck | Partnership

The $2.5 billion deal is centered around the development of an exclusive degrader ADC, with the added option to license three additional degraders. C4's platform is dedicated to targeted protein degradation, employing two types of degraders to expand the scope of proteins addressed. This collaboration signifies Merck's fourth partnership with C4, building on prior agreements with Biogen and Roche.

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Avidity Biosciences Reports Positive Data for AOC 1044 in DMD | Clinical Trial

The positive data emerging from the Phase 1 trial for AOC 1044, an Antibody Oligonucleotide Conjugate designed for Duchenne muscular dystrophy treatment, revealed concentrations of phosphorodiamidate morpholino oligomers (PMO) in skeletal muscle up to 50 times greater than peptide-conjugated PMOs after a single dose in all healthy volunteers. Avidity has set its sights on revolutionizing RNA therapeutics through its AOC platform, simultaneously advancing AOC 1001 and AOC 1020 for DM1 and FSHD, respectively.

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Nano Biosciences Enters an Agreement with Pfizer | Partnership

After its acquisition of Seagen, Pfizer has forged a $1.1 billion agreement with Nona Biosciences, pledging $53 million in upfront and near-term payments for the exclusive global license of HBM9033, a mesothelin-targeted ADC. This strategic deal enhances Pfizer's standing in the ADC sector, a high-potential area identified by its CEO in recent business development discussions.

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Sanofi Ends the Development of Its Only Clinical ADC | Clinical Trial

The company encountered a major setback as it decided to discontinue its only clinical ADC, tusamitamab ravtansine, following disappointing Phase III results in the treatment of second-line metastatic NSCLC. Despite the potential for improved overall survival, the company chose to wind down the entire development program, originally scheduled for a 2024 submission. However, Sanofi remains committed to exploring other ADC candidates based on tusamitamab and investigating CEACAM5 as a potential biomarker in highly expressed cancers.

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LegoChem and Janssen Enter a License Agreement | Partnership

LegoChem Biosciences has entered into a $1.7 billion deal with Janssen Biotech, licensing LCB84, a Trop2-targeted ADC. Janssen will be granted exclusive global rights for LCB84, assuming responsibility for clinical development and commercialization following the ongoing Phase 1/2 trials. Currently undergoing Phase 1/2 clinical trials, LCB84 demonstrates high potential in targeting Trop2 on multiple solid tumors.

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Gene Therapy

Atsena Releases Positive Results from PhI/II for LCA1 Candidate | Clinical Trial

Atsena Therapeutics has reported positive 12-month results from its Phase I/II trial of ATSN-101, their candidate for Leber congenital amaurosis (LCA1). The trial involved 15 patients aged 12 to 76, with no serious adverse events reported at the highest dose. The treatment demonstrated clinically meaningful improvements in vision, and the company is exploring partnership options to advance the therapy into a pivotal trial. Several other companies are advancing candidates in clinical trials, including MeiraGTx. 

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uniQure Provides Another Look at Huntington’s Candidate | Clinical Trial

uniQure has disclosed updated interim data on its gene therapy, AMT-130, designed for Huntington's disease treatment. The information includes up to 30 months of follow-up from 39 patients enrolled in the ongoing Phase I/II clinical trials in the United States and Europe. Despite a small sample size and no placebo control group, the company highlighted positive trends, indicating preserved neurological function, dose-dependent clinical effects, and reductions in the neurofilament light chain—a Huntington's-associated biomarker. This builds on previous data released in June, which was noisy. uniQure plans regulatory discussions in the new year.

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MeiraGTx Sells Rights to AAV5-RPGR to J&J for up to $415M | Partnership

MeiraGTx has entered into an asset purchase agreement with Janssen Pharmaceuticals, Inc. (J&J), a Johnson & Johnson company, for the remaining interests in bota-vec, a gene therapy for XLRP. The deal includes an initial $130 million upfront and near-term milestone payments, with potential additional payments of up to $285 million upon first commercial sales of bota-vec in the U.S. and EU. The agreement also involves a commercial supply agreement and a technology transfer agreement for bota-vec manufacturing. The company had previously planned on filing a BLA for bota-vec in 2024. 

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Takeda Ends Partnership with JCR as Former Deprioritizes AAV | Partnership

Takeda has decided to end its collaboration with JCR Pharmaceuticals just as the latter has achieved proof of concept for its gene therapy technology, J-Brain Cargo, designed to penetrate the blood-brain barrier. Takeda has been intensifying its therapeutic strategy that has seen it move away from viral gene therapies. JCR will now seek new partnerships to advance its gene therapy research, aiming to expand beyond lysosomal storage disorders into neurological diseases. 

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4DMT Receives RMAT Designation from FDA for Wet AMD Candidate | Regulatory

4DMT has received RMAT designation from the FDA for its investigational candidate, 4D-150, for the treatment of wet age-related macular degeneration (wet AMD). The RMAT designation facilitates expedited development and review, providing benefits akin to fast track and breakthrough therapy programs. 4D-150 aims to maintain long-term visual acuity outcomes in wet AMD patients, eliminating the need for repeated intravitreal injections. 4DMT’s candidate is behind RegenxBio’s, which is in Ph3 testing with a planned BLA in 2024.

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Oligo 

SanegeneBio and Innovent Enter Partner to Develop Hypertension siRNA Therapies | Partnership

Sanegene Bio USA Inc. and Innovent Biologics, Inc. made a joint announcement about their collaboration to develop SGB-3908, an siRNA drug designed to target angiotensinogen (AGT) for the treatment of hypertension. Innovent secures an exclusive option for future licensing, covering the potential rights for the development, manufacturing, and commercialization of SGB-3908. With SanegeneBio's LEAD™ platform and Innovent's clinical proficiency, the collaboration aims to fast-track the development process and ensure the effective deployment of this innovative siRNA drug, offering promising prospects for hypertension patients.

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A First-in-Class Inhaled mRNA for Respiratory Viral Infections Enters Phase 1 Study | Clinical Trial

Ethris GmbH has received approval from the United Kingdom (U.K.) Medicines and Healthcare Products Regulatory Agency (MHRA) and will initiate a Phase 1 clinical trial for its inhaled mRNA candidate, ETH47. This innovative program aims to address respiratory viral infections through a locally administered mRNA-based product candidate featuring type III interferon, developed using Ethris' Stabilized Non-Immunogenic mRNA (SNIM®RNA) platform. Supported by the BayTherapie2020 program, ETH47's Phase 1 study is set to begin in the U.K. in December.

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Moderna Publishes Pivotal Phase 3 Clinical Data on Investigational RSV Vaccine, MRNA-1345, in New England Journal of Medicine | Clinical Trial

Moderna, Inc. has globally submitted marketing authorizations for mRNA-1345 and is actively preparing for a projected 2024 marketing launch. The positive Phase 3 clinical study results for mRNA-1345, Moderna's vaccine candidate for respiratory syncytial virus (RSV), have been published in The New England Journal of Medicine, emphasizing safety and efficacy data from the ConquerRSV trial. If approved, mRNA-1345 is expected to be the only ready-to-use RSV vaccine available in single-dose prefilled syringes, addressing this highly contagious virus.

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Arrowhead Pharmaceuticals Seeks Regulatory Approval to Commence Phase 1/2a Trial of ARO-CFB in Complement-Mediated Kidney Disease | Clinical Trial 

Arrowhead Pharmaceuticals Inc. has formally applied to commence a Phase 1/2a clinical trial for ARO-CFB, their investigational RNA interference (RNAi) therapeutic developed as a potential remedy for complement-mediated renal diseases, notably immunoglobulin A nephropathy (IgAN). ARO-CFB aims to diminish hepatic expression of complement factor B (CFB), a pivotal regulator in amplifying complement alternative pathway activation, offering promise as a treatment option for complement-mediated renal diseases pending clearance for the clinical trial.