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The single doses were nothing to write home about, and only one patient enrolled so far for the multiple doses https://www.globenewswire.com/news-release/2024/06/03/2892097/0/en/Century-Therapeutics-Presents-Interim-Results-from-Phase-1-ELiPSE-1-Study-at-ASCO-2024-Annual-Meeting.html
Poster https://www.centurytx.com/wp-content/uploads/20240517_Century_ASCO_FINAL.pdf
ASGCT PR https://finance.yahoo.com/news/century-therapeutics-presents-preclinical-data-110000872.html
The other poster
Last year Clade Therapeutics announced the acquisition of Gadeta B.V. https://www.globenewswire.com/news-release/2023/10/02/2752753/0/en/Clade-Therapeutics-Announces-the-Acquisition-of-Gadeta-B-V.html
Gadeta was developing cell therapies expressing defined gamma-delta T-cell receptors that specifically recognise cancer cells. In order to harness the unique targeting properties of gamma-delta TCRs, Gadeta developed the TEG platform, which equips alpha-beta T-cells (used in the production of CAR and TCR therapies) with a defined gamma-delta TCR https://www.sciencedirect.com/science/article/pii/S0006497120448153
Gadeta also developed a novel proprietary gamma-delta TCR discovery engine based on a 'TCR centric' selection approach that sourced patient material (for a broad range of naturally selected gamma-delta TCRs from different tissues), screened (to identify tumour reactive gamma-delta TCRs from co-cultures of patient material) and selected gamma-delta TCRs optimal properties. Some preclinical data https://aacrjournals.org/cancerres/article/82/12_Supplement/2818/701504/Abstract-2818-Targeting-solid-tumors-with-GDT002-a
Upcoming (Fri, May 10) https://annualmeeting.asgct.org/program/agenda-speaker-details?agendaId=37279
As for the antibody degrader, I don't see them being able to combine the cells with therapeutic antibodies. But they might not need to add it.
Doesn't look that way with auto CAR-T. Out of the 15 treated, all had auto-antibodies, with 13 in skin, 11 in lung, 9 in kidney, 9 in joints, 4 in the heart, 3 in muscle, and other organs. Renal (kidney) disease occurs in up to 40% of patients and can evolve to kidney failure requiring dialysis and is associated with higher risk of death.
CSO was smart selling off his shares. Depleting B cells is not investable, trading in SLE for B cell aplasia is a good deal?
The PR https://www.biospace.com/article/releases/century-therapeutics-presents-initial-data-from-cnty-101-phase-1-elipse-1-trial-supporting-the-potential-for-a-multi-dosing-strategy-for-car-ink-enabled-by-allo-evasion-edits/
Poster https://www.centurytx.com/wp-content/uploads/2023-ASH-poster_Century-Tx_FINAL.pdf
Summary of the case that is going to be presented at ASH https://ash.confex.com/ash/2023/webprogram/Paper182313.html
Patient with high-risk R/R follicular lymphoma. Completed four 28-day cycles of CNTY-101 at the 100 million cell dose (DL1), first two administered following lymphodepletion, while the most recent two were administered without lymphodepletion. All doses of CNTY-101 with and without IL-2 or LD were well tolerated and demonstrated clinical benefit as defined as stable disease or better (per Lugano 2014 criteria). Responses were associated with tumour shrinkage and an ongoing CR of a duration of five months since the first CNTY-101 infusion. The PK data showed that CNTY-101 cells were detected after each infusion with comparable kinetics, with a limited duration in circulation. No measurable CDC-inducing functional ADA detected in any samples by data cut-off (including the first three cycles). Treatment was associated with changes in tumour microenvironment within eight days post-infusion, augmentation of adaptive T-cell responses, and tumour shrinkage.
CSO sold off his shares not sure why
Extensive epigenetic and transcriptomic donor-specific differences observed in iPSC derived allogenic NK (iNK) cells https://www.abstractsonline.com/pp8/#!/10828/presentation/6083
iPSC-derived CAR-NK cell therapy: nominating clinical candidate clones through integrated multi-functional analysis https://www.abstractsonline.com/pp8/#!/10828/presentation/3328
The company will host a virtual Research and Development Day on Friday, Nov 11, from 8:00 AM to 9:30 AM ET. The R&D Day will feature presentations from the management team and Jonathan Rosenberg, M.D., Chief of the Genitourinary Oncology Service at the Memorial Sloan Kettering Cancer Center, Physician at Memorial Hospital, and Professor of Medicine at Weill Cornell Medical College. The event will focus on the company's solid tumour strategy and gamma delta iT cell platform, including a discussion on preclinical data to be presented at the Society for Immunotherapy of Cancer Annual Meeting.
SITC titles
Empowering iPSC-Derived iNK Cells with Multiple Gene Edits to Improve Persistence and Anti-Tumor Efficacy
Multiple Targeting of Solid Tumors with iPSC-derived Gamma Delta CAR T Cells in Combination with Therapeutic Antibodies
Yes, and the expansion cohorts will include both CAR-T naïve and relapsed. Next data from them should be around Dec, so ASH or an investor event. They have decided not to go past 1.5B cells per dose (x three doses) for some reason. Based on the data so far there is a dose response relationship (300M or 1B per dose) and all CRs are ongoing.
They should. High-affinity CD16 variants in the population correlate with clinical outcomes, so better objective responses and progression-free survival. However, the CD16 receptor is cleaved from the surface of activated NK cells, which leads to dysfunction and reduced antibody-dependent cellular cytotoxicity.
FATE could present some early clinical data on both at FT538 and FT536 at SITC. The former is being tested in combo with mAbs, while the latter (has an added CAR, along with the same three edits* as the other) is as a single agent or with mAbs.
* https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00350-7
NKTX seems to repeat what DTIL tried with 19a/eLD. Why they don't increase the NK cells dose to 4 billions same as AUTO NK?
Will the ISPC NK cells work if the mAb is the weakest link? .AFM24 v. cetuximab hold the key to success?
AZ just stopped the trial of monalizumab in combination with cetuximab vs. cetuximab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).
According to a medical doctor on twitter they haven't been able to secure a source for the cbNKs. A second Fc receptor, CD64, binds to the same IgG's as CD16a, but with more than a 30-fold higher affinity. However, it is typically only expressed on myeloid cells, not NKs. FATE created a recombinant receptor consisting of the extracellular region of CD64 with transmembrane and intracellular regions of CD16a. Not only did they show activity, but additionally, the higher affinity of allowed for mAbs to be pre-adsorbed and improved targeting without additional mAb use. Also, they could still mix and match mAbs as well https://ashpublications.org/blood/article/136/Supplement%201/10/470430/Engineered-iPSC-Derived-NK-Cells-Expressing
AFMD seemed to have solved the cleaved CD16 issue by pretreating the NK with their AFM13 ex-vivo.
Looking at P1 data from Fate and NKTX, NK cells seem to be effective on indolent lymphoma and nodal DLBCL. For pts with high tumor burden or aggressive disease, CART will still be needed. I listened to NKTX presentation, the number of cycles given to a patient will be up to the oncologist.
Dr. Kaufman has presented some preclinical data
Has anyone compared ISPC NK to CBNK?
A virtual R&D update will be held on June 13, at 4:30 PM ET. Century's management will discuss CNTY-103 and progress on the next-generation platform. Dr Sheila Singh, Professor of Surgery and Biochemistry, Chief Paediatric Neurosurgeon at McMaster Children’s Hospital, the Division Head of Neurosurgery at Hamilton Health Sciences, and the inaugural Director of McMaster's new Cancer Research Centre will discuss the current treatment paradigm in GBM.
952: Enabling the Engineering of iPSC Based Cell Therapies Using MAD7, a Novel CRISPR Nuclease https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=1867
ASGCT title:
Enabling the Engineering of iPSC Based Cell Therapies Using MAD7, a Novel CRISPR Nuclease.
Preclinical data on mbIL-15 https://ashpublications.org/blood/article/124/7/1081/33687/Autonomous-growth-and-increased-cytotoxicity-of
NKG2A https://www.jci.org/articles/view/123955
PET https://jnm.snmjournals.org/content/61/9/1348.long
As for allo evasion, it could be CD47 https://rupress.org/jem/article/218/3/e20200839/211668/The-SIRP-CD47-immune-checkpoint-in-NK-cellsSIRP
Data Disclosures
MAD7 nuclease in iPSC gene editing platform (2Q).
Epigenetics and cell reprogramming (2H).
CNTY-102 (4Q).
iNK platform 2.0 (4Q).
Events
R&D Day (GBM, CNTY-103 and Universal CAR) (1H).
R&D Day (TBD) (4Q).
PR https://www.globenewswire.com/news-release/2021/12/16/2353430/0/en/Century-Therapeutics-Announces-Presentation-of-Data-at-the-63rd-American-Society-of-Hematology-Annual-Meeting-and-Provides-Pipeline-Updates.html
Slides https://investors.centurytx.com/static-files/517375cf-023b-4926-bd42-a0e3e7e8708e
R&D Update (Dec 16, from 8:00 AM to 9:30 AM EST)
Link to webcast https://kvgo.com/corporate-services/century-therapeutics-r-d-2021
ASH abstracts
Development of Multi-Engineered iPSC-Derived CAR-NK Cells for the Treatment of B-Cell Malignancies https://ash.confex.com/ash/2021/webprogram/Paper148438.html
Induced Pluripotent Stem Cell-Derived Gamma Delta CAR-T Cells for Cancer Immunotherapy https://ash.confex.com/ash/2021/webprogram/Paper149095.html
They are also working on an iT (BCMA + undisclosed) for myeloma, iNK or iT (multi-specific) for bladder, iNK or iT (multi-specific) for ovarian, iNK or iT (multi-specific) for RCC, and iNK or iT (multi-specific) for HCC.
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