Adaptimmune Therapeutics PLC (ADAP) Quote

The question remains, was it due to a refocused R&D strategy or data driven.

Upcoming Investor Day (Apr 18, 8:00 am EDT) https://adaptimmune.zoom.us/webinar/register/WN_SAFMQyw3QbiyM9wSLIaTqw#/registration

The multi-year strategic collaboration they struck with RHHBY's Genentech has been terminated. The agreement, established initially for eight years, aimed at launching cell therapies for various cancer indications using ADAP's iPSC platform. Per the terms, ADAP received $150M upfront and was expected to receive $150M in additional payments over five years. ADAP was also eligible to receive development and other milestone-based payments totalling as much as $3B.

https://finance.yahoo.com/news/strategic-collaboration-between-adaptimmune-genentech-120000529.html

There is going to be clinical data from LYEL, CRSP and Arsenal Bio* over the next few years that could show if T-cell ''exhaustion'' can be overcome.

* The synthetic pathway activators that Arsenal Bio have created help with maintenance of T-cell stem-like phenotypes, and restrict accessibility of various exhaustion marker genes

ADAP under $2

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ADAP...BIO MONSTER COMING IN HERE

ADAP new 52 week high

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ADAP under $2

This explains why TIL, TCR-T, Tigit, ... not working. Exhausted T is a misnomer
https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00040-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124724000408%3Fshowall%3Dtrue

WOOOOW 27000 SHARE BUY $$$$$$$$$$$

Adaptimmune Announces U.S. FDA Acceptance of Biologics License Application for Afami-cel for the Treatment of Advanced Synovial Sarcoma with Priority Review
Newsfile Corp.
Newsfile Corp
If approved, afami-cel will be the first engineered T-cell therapy for solid tumors and the first effective treatment option for synovial sarcoma in more than a decade
Philadelphia, Pennsylvania and Oxford, United Kingdom--(Newsfile Corp. - January 31, 2024) - Adaptimmune Therapeutics plc (NASDAQ: ADAP), a company redefining the treatment of solid tumor cancers with cell therapy, today announced that the U.S. Food and Drug Administration (FDA) has accepted for priority review its Biologics License Application (BLA) for afami-cel, an investigational engineered T-cell therapy for advanced synovial sarcoma. The application has a Prescription Drug User Fee Act (PDUFA) target action date of August 4, 2024.

Adrian Rawcliffe, Adaptimmune's Chief Executive Officer: “The FDA’s acceptance of the BLA submission brings us one step closer to redefining treatment for people with synovial sarcoma. Our franchise has great potential and, if approved, we have the capabilities and the capital to launch afami-cel - the first engineered T-cell therapy on the market for a solid tumor cancer.”

Dennis Williams, PharmD, Senior VP of Late-Stage Development: "Historic outcomes are poor for advanced synovial sarcoma, with low objective response rates for second-line therapies and overall survival of less than 12 months for people who have received two or more prior lines of therapy. In clinical trials, afami-cel has demonstrated an impressive response rate of ~39% among heavily pre-treated patients with advanced synovial sarcoma and about a 17-month median survival. This regulatory milestone is a testament to our teams' relentless work to deliver a novel treatment option to more people diagnosed with synovial sarcoma."

This acceptance is supported by positive data from Cohort 1 of the pivotal trial SPEARHEAD-1, which met its primary endpoint for efficacy. Data from the trial were presented at the Connective Tissue Oncology Society (CTOS) 2023 Annual Meeting.

when was the last time the mgt. didn't missed a milestone promised. BLA, PRAME, ...

Hard to say, but they have only talked about sequential/combination treatment with afami-cel and lete-cel, not committed to it. Based on what others are doing, I would like them to pick up the pass of innovation. Based on their own data, a TGF-B signature was measured across tumour indications, so think they should test the combination of NY-ESO-1 with MAGE-A4 TCRs that co-express the CD8a co-receptor with a dnTGF-BRII as well. They also ran a sub-study testing afami-cel with low-dose radiation. While small, it did show greater detection of SPEAR T-cells in tumour biopsies when infusion followed it. As for TC-520 (targeting CD70), I think it should be dropped.

May be the investors realized that CART, CARNK targeting single antigen not going to subdue solid cancers. Will 2nd gen SPEAR cells NY-ESO + MAGE-A4 combo or extracellular CD70 + SPEAR T cells combo avoid the CAR crash?

Has the CEO finally awoken?!

''Sarcoma franchise of afami-cel and lete-cel leverages same development and commercial footprint with US peak year sales projected to be up to $400 million

BLA submitted in 2023 for afami-cel; projected acceptance by US FDA in Q1 2024

Company preparing for US launch of afami-cel in 2H 2024 upon expected approval

Pivotal trial for lete-cel met its primary endpoint for efficacy; full data set
in Q3 2024

Company working toward approval of lete-cel; planning for US commercial launch in 2026

Company funded into early 2026 with > $300 million including existing balance sheet, projected payments from partners, and other non-dilutive capital sources'' https://finance.yahoo.com/news/adaptimmune-projects-sarcoma-franchise-deliver-123700704.html

CARTs, ADCs not investable. Too many to count. Targeted bombing offers no OS benefits but long term health issues, secondary cancers and infections.

https://www.managedhealthcareexecutive.com/view/adaptimmune-completes-bla-for-cell-therapy-for-solid-tumors

Hard to say, but in the next few I expect to see datasets from others trials (testing ADCs) in platinum-resistant ovarian. However, there are downsides including, TEAEs, such as those leading to drug discontinuation, interruption or reduction. Also, dosing every 'x' amount of weeks.

ADAP new 52 week low

Very nice read

Thanks for posting

The PR https://finance.yahoo.com/news/adaptimmune-reports-positive-data-lete-120000366.html

PDF https://d1io3yog0oux5.cloudfront.net/_344920efd0af3676fab777bf7e089512/adaptimmune/files/pages/adaptimmune/db/336/description/ny-eso-1/IGNYTE_substudy-1_CTOS23.pdf

I wonder why they no longer talk about overexpression of PDE4C or PDE7A (the latter increases the ability to induce apoptosis in target cells, confers (partial) resistance to the inhibitory effects of forskolin, PGE2 and adenosine, as well as (partially) resistance to the inhibition of cytokine release by mediators that increase intracellular cAMP). Also, inducible IL-7 and inducible IL-15

https://www.biospace.com/article/releases/adaptimmune-selects-adp-600-as-clinical-candidate-for-best-in-class-prame-strategy/

They should have taken a next-gen version* into the clinic instead. This is based on where IMTX is and the data generated to date https://investors.immatics.com/static-files/138d7b76-d252-4c61-a824-e17307c4f537

* I think it should include a CD8a co-receptor and dominant-negative TGF-B receptor https://journals.aai.org/jimmunol/article/208/1/169/234163/Engineering-Cancer-Antigen-Specific-T-Cells-to

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Preclinical https://link.springer.com/article/10.1007/s00262-023-03556-7

New NY-ESO-1 data https://ctos2023.eventscribe.net/index.asp?posterTarget=604312

This is not good enough to survive the ADC tsunami.
35.6% (2 complete response, 14 partial response [PR]). Median duration of response was 20.79 weeks (95%CI: 11.6, 30.9)

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The ESMO abstract

1019O - Clinical and translational data from the phase I SURPASS trial of ADP-A2M4CD8 T cell receptor (TCR) T cell therapy alone or combined with nivolumab in solid tumors

Background
ADP-A2M4CD8 is a TCR T-cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), modified with a CD8a coreceptor, to treat human leukocyte antigen A*02–eligible patients (pts) with unresectable/metastatic solid tumors. ADP-A2M4CD8 monotherapy has demonstrated an acceptable benefit-to-risk profile and encouraging anti-tumor activity in the ongoing phase 1 SURPASS trial. Nevertheless, inhibition of immunosuppressive pathways may improve anti-tumor responses; therefore, new SURPASS cohorts include ADP-A2M4CD8 combined with nivolumab or pembrolizumab. We report data from pts receiving monotherapy and nivolumab combination therapy.

Methods
T-cells are obtained by leukapheresis, transduced with a lentiviral vector carrying the TCR and CD8a coreceptor genes, expanded ex vivo, and infused back to the pt following lymphodepleting chemotherapy. ~Four weeks after ADP-A2M4CD8 infusion, a subset of pts also received nivolumab 480 mg every 4 weeks until unacceptable toxicity/disease progression. Primary and secondary objectives are safety and anti-tumor activity, respectively.

Results
As of March 9, 2023, 51 pts with a median age of 60 years (range: 31–75) mainly with melanoma, non-small cell lung, ovarian, gastroesophageal, head and neck, or urothelial cancers received 1.02–9.95x109 ADP-A2M4CD8 T-cells. Median (range) number of prior lines of therapy was 3 (1–8) and MAGE-A4 expression H-score was 250 (90–300). The four most common adverse events related to T-cell therapy were cytokine release syndrome (n=38 [74.5%]; 7 [13.7%] were Grade≥3), neutropenia (27.5%), pyrexia and fatigue (each 21.6%). Overall response rate per RECIST v1.1 by investigator review in monotherapy pts (n=45) was 35.6% (2 complete response, 14 partial response [PR]). Median duration of response was 20.79 weeks (95%CI: 11.6, 30.9). In pts assigned to nivolumab combination (n=6), there was 1 PR, 3 stable disease, and 2 not evaluable (2 pts have not received nivolumab and have no post-baseline RECIST assessment). Data from additional pts treated by August 2023 will be presented.

Conclusions
ADP-A2M4CD8 continues to show an acceptable benefit-to-risk profile, including in pts receiving nivolumab combination therapy.

ADAP new 52 week low

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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!

ADAP new 52 week low

👉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

ADAP new 52 week low

It's now recruiting.

(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

(OT): Interesting approach. I wonder if the efficacy could be improved by altering the phenotype of the recruited M2-like macrophages https://www.biorxiv.org/content/10.1101/2023.06.20.545790v1

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

ASCO

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.

Upcoming https://annualmeeting.asgct.org/program/agenda-details?agendaId=26880

(OT) Two interesting preclinical papers https://jitc.bmj.com/content/11/4/e005519 https://www.frontiersin.org/articles/10.3389/fimmu.2023.1062365/full

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