Q2 results https://finance.yahoo.com/news/adaptimmune-reports-second-quarter-financial-112900334.html
BLA completion moved to Q4. PRAME IND also pushed forward to later this year (I guess Q4 as well). Nothing on lete-cel (NY-ESO-1). Also, SURPASS data at ESMO in October. However, the CMO said there would be only a few more monotherapy patients, with early data in around ten (across all indications) in combination with Opdivo. Sounds like expectations are low as he added, "remember that this is also in late stage patients who have been heavily pre-treated.'' Apart from that it's all good!
👉Innovative new cell therapy approach makes its clinical debut: Integration of a CAR binding domain into the native TCR signaling complex (TRuC CAR) is associated with objective antitumor responses + on-target toxicities in mesothelin-expressing cancers. https://t.co/ZUG8jtMSpS— Klebanoff_Lab (@KlebanoffLab) July 27, 2023
(OT): Combination of NY-ESO-1 TCR-T cells co-engineered to secrete SIRP-alpha decoys with antitumour antibodies to augment macrophage phagocytosis https://www.biorxiv.org/content/10.1101/2023.06.27.546523v1
Case report https://journals.lww.com/melanomaresearch/Fulltext/9900/Durable_control_of_metastases_in_an_HLA_A2_.63.aspx
They should have continued with this sub-study https://d1io3yog0oux5.cloudfront.net/adaptimmune/files/pages/adaptimmune/db/336/description/DP006-21A_Adaptimmune_SITC_2021_Welsh_Radiation_Substudy_Poster_final.pdf
Adaptimmune Announces 70% of People with Advanced Synovial Sarcoma Who Respond to Afami-cel are Alive Two Years Post-Treatment; Data from Cohort 1 of SPEARHEAD-1 to be Presented at ASCO https://finance.yahoo.com/news/adaptimmune-announces-70-people-advanced-210000466.html
The SPEARHEAD-1 trial of afamitresgene autoleucel (afami-cel [formerly ADP-A2M4]): Analysis of overall survival in advanced synovial sarcoma https://meetings.asco.org/abstracts-presentations/219898
The SPEARHEAD-1 trial of afamitresgene autoleucel (afami-cel [formerly ADP-A2M4]): Pooled analysis of cytokine release syndrome across cohorts in patients with advanced synovial sarcoma https://meetings.asco.org/abstracts-presentations/224954
From FB https://www.fiercepharma.com/pharma/astellas-writes-340m-fibrogens-evrenzo-joins-gsk-nixing-cell-therapy-collab-adaptimmune
''In another R&D rewinding, Astellas is ending a partnership with Adaptimmune Therapeutics around stem cell-derived, off-the-shelf T cell therapies. The termination deals another blow to Adaptimmune as GSK just walked away from their cell therapy collaboration as well.''
The company said it will regain rights to the PRAME and NY-ESO-1 programs from GSK. Adaptimmune will receive an upfront payment plus milestone-based payments totalling £30M related to the transfer of the clinical trials for the NY-ESO-1 programs.
The companies will transition materials and data related to the preclinical PRAME targeted TCR T-cell therapy program to Adaptimmune during 2023. The companies are targeting transfer of sponsorship for GSK's IGNYTE-ESO trial (NCT03967223) and long-term follow-up (NCT03391778) during Q3. The companies noted that all other trials within the NY-ESO-1 targeting program are already closed to enrollment and have already been or will soon be completed by GSK.
Afamitresgene autoleucel (afami-cel; formerly ADP-A2M4) demonstrates durable clinical responses by inducing broad immune engagement with anti-tumor activity https://www.abstractsonline.com/pp8/#!/10828/presentation/3024
The good: There have been new responses, which has increased the ORR to 52% (from 44%) in heavily pre-treated patients with late-stage ovarian, urothelial, and head & neck cancers after single dose of ADP-A2M4CD8. Across the entire ongoing SURPASS trial, the ORR has increased to 37% (from 33%), and the median duration of response has increased to ~20 weeks (from ~12 weeks) since the last update.
In ovarian, the ORR has increased with one new response and the company recently received FDA RMAT Designation. Also, the ORR has increased in urothelial with one new complete response. A new cohort in SURPASS will planned the combination with a checkpoint inhibitor in the second-line setting. In addition, another new cohort will test the combination with first-line standard of care in head & neck cancer.
The bad: They will stop the SURPASS-2 and TIL trials. Cease further investment in additional non-core activities, including work on preclinical projects, such as the HiT program, additional TCRs, and broader HLA coverage. Also, delay investment in the commercialisation of afami-cel based on the BLA timelines. In addition, the iPSC-derived MAGE-A4 program won't enter the clinic until at least 2025. On top of that, until they understand the terms of the transfer from GSK and the data package, will not invest in lete-cel, targeting NY-ESO-1. Finally, lay off up to 30% of staff. This will extend cash runway into 2025.
Cell Therapies need eganelisib for TME and durability.
The results from first gen trial have been out for a while
Could be a strategic decision to pull out of cell therapy and focus on other areas in oncology and to move resources into vaccines for example.
GSK is transferring back the NY-ESO-1 and PRAME programs. This was due to a ''strategic review'' following lete-cel data in NSCLC.
In 2014, the two signed a collaboration and license agreement, for up to five programs. In 2017, GSK exercised its option to exclusively license the right to develop and commercialise NY-ESO-1, after which two more targets, including PRAME, were nominated.
Adaptimmune said it is expected that that the license agreement will now terminate, and GSK will not have any rights to nominate any additional targets. The terms of the transfer are being negotiated; the company added. Adaptimmune noted that GSK will deliver data from an ongoing PhII (registration-directed) trial with lete-cel in STS with final data expected in 2023.
Adaptimmune said it will continue to prioritise and focus on its lead MAGE-A4 franchise while deciding an optimal development path for the other assets.
Yes, but they had failed a number of lines (median was three), so the safety was acceptable. They already have an ongoing (registration-directed) PhII in esophageal and esophagogastric junction, with another (for ovarian) planned this year. If you take the latter, the ORR so far is 36% and DCR is 86%, while the current ORR for existing therapies in platinum-resistant disease is under 13%.
Same as DTIL 19A.
There were 2 deaths reported as related to ADP-A2M4CD8 by investigators. A 60-year-old woman with ovarian cancer with a large tumor burden in her lungs died due to pneumonia and CRS. As reported at ESMO 2021, a 71-year-old man with adenocarcinoma of the esophagus and a history of chronic anemia died due to bone marrow failure.
NEA just ran GNCA to the ground. Sending ADAP VP to GNCA was a gimmick.
Posters https://d1io3yog0oux5.cloudfront.net/adaptimmune/files/pages/adaptimmune/db/336/description/preclinical/DP008-22A_Crowther_TILIL7_Poster_ASGCT_2022_Final_Print.pdf https://d1io3yog0oux5.cloudfront.net/adaptimmune/files/pages/adaptimmune/db/336/description/preclinical/DP008-22A_Pope_ADP-A2M4N7X19Poster_ASGCT_2022_Final_Print.pdf
335: Next-Generation, Inducible IL-7-Expressing, Tumor-Infiltrating Lymphocytes by Lentiviral Vector Genetic Modification for Clinical Application https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=1289
385: IL-7 and CCL19 Expression in Specific Peptide Enhanced Affinity Receptor T-cells Targeting MAGE-A4 Display Improved Survival and Ability to Induce Migration of Immune Cells https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=1335
1168: A Novel Flow Cytometry Method for Rapid Assessment of Lentiviral Detection https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=2064
Next-Generation, Inducible IL-7-Expressing, Tumor-Infiltrating Lymphocytes by Lentiviral Vector Genetic Modification for Clinical Application.
IL-7 and CCL19 Expression in Specific Peptide Enhanced Affinity Receptor T-cells Targeting MAGE-A4 Display Improved Survival and Ability to Induce Migration of Immune Cells.
A Novel Flow Cytometry Method for Rapid Assessment of Lentiviral Detection.
AACR PR https://www.globenewswire.com/news-release/2022/04/08/2419433/35803/en/Adaptimmune-Presents-MAGE-A4-Expression-Data-from-its-Screening-Protocol-at-AACR-Confirming-Expression-Across-a-Broad-Range-of-Solid-Tumors.html
New preclinical data https://www.jimmunol.org/content/early/2021/12/01/jimmunol.2001357.long
GSK's GSK3845097 (one of three next-gen versions they both worked on together*), which co-expresses a dominant-negative TGF-ß type II receptor and targets NY-ESO-1 is in the clinic.
* So is another, the CD4+ T-cells co-express a CD8 co-receptor (again, it targets NY-ESO-1). The third isn't in the clinic, but it could overexpress PDE7A (increases resistance to both PGE2/adenosine and enhances apoptosis in target cells).
A trial (along with at least two others) testing this in the next-gen MAGE-A4 TCR-T product should open sometime next year.
Another, Enhanced Activity of Second-Generation MAGE-A4 SPEAR T-Cells Through Co-Expression of a CD8a Homodimer https://s3.amazonaws.com/content.stockpr.com/adaptimmune/files/pages/adaptimmune/db/212/content/AACR+2019+MAGE-A4+Preclinical+poster+FINAL.pdf
The ovarian patient with a confirmed CR had a high MAGE-A4 expression with 95% tumour cells with 3+ staining. Adding decitabine (hypomethylating agent and a potent inducer of TAAs) could selectively modulate TAA expression in TAA low-expressing tumour cells and enhance the therapy https://d201nm4szfwn7c.cloudfront.net/5f95dbd7-245e-4e65-9f36-1a99e28e5bba/7d9a26ec-fef3-42fb-b671-2a8889398f09/7d9a26ec-fef3-42fb-b671-2a8889398f09_viewable_rendition__v.pdf
Here is the video