Adaptimmune Therapeutics PLC (ADAP)

[jondoeuk]

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

[jondoeuk]

Preclinical data https://journals.lww.com/immunotherapy-journal/Fulltext/9900/Enhancing_Efficacy_of_TCR_engineered_CD4__T_Cells.44.aspx

[jondoeuk]

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.

[jondoeuk]

SURPASS-3 is now listed https://clinicaltrials.gov/ct2/show/NCT05601752

[NY1972]

Cell Therapies need eganelisib for TME and durability.

[jondoeuk]

The results from first gen trial have been out for a while
https://clinicaltrials.gov/ct2/show/results/NCT02588612?term=gsk+nyeso&draw=2&rank=2&view=results

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.

[jondoeuk]

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.

[jondoeuk]

Upcoming https://cattendee.abstractsonline.com/meeting/10720/presentation/1291

[jondoeuk]

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%.

[NY1972]

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.

[jondoeuk]

PR https://www.biospace.com/article/adaptimmune-reports-positive-data-in-its-surpass-trial-outlines-plans-for-advanced-clinical-development-in-multiple-mage-a4-positive-solid-tumors/

Slides https://d1io3yog0oux5.cloudfront.net/_f617782e4202c5521b46a5b8f77036e5/adaptimmune/db/249/3527/pdf/ESMO+Clinical+and+Development+slides-final.pdf

[jondoeuk]

The ESMO abstract is out, with an ORR of 31% and DCR of 75.9% (data cutoff was Dec '21 with 29 patients). The previous data was an ORR of 36% and DCR of 86% (22 patients).

[jondoeuk]

Link to register https://bit.ly/3QBacNt

[jondoeuk]

On the 9th of Sept, the company will host a live, virtual event to review the PhI SURPASS trial data (that will be presented as a mini oral at ESMO), and outline plans for further development of the SURPASS family of trials.

[dhbuzz]

Just got in,see there is a lot of insider buying.
GLTA

[bandit007]

Looks like this could run. Took a position

[NY1972]

NEA just ran GNCA to the ground. Sending ADAP VP to GNCA was a gimmick.

[jondoeuk]

PR https://www.globenewswire.com/news-release/2022/05/16/2444402/35803/en/Preclinical-Proof-of-Concept-Data-Supporting-Future-Clinical-Development-of-Two-New-Cell-Therapies-Being-Presented-by-Adaptimmune-at-ASGCT.html

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

[jondoeuk]

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

[jondoeuk]

ASGCT titles:

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.

[jondoeuk]

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

Poster https://d1io3yog0oux5.cloudfront.net/adaptimmune/files/documents/20210428/Wang_HLA_and_MAGE-A4_Screening_Poster_AACR2022_Final_Print.pdf

[jondoeuk]

Also, they aim to open the allogeneic facilities by the end of the year.

[jondoeuk]

Upcoming

[jondoeuk]

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).

[jondoeuk]

A trial (along with at least two others) testing this in the next-gen MAGE-A4 TCR-T product should open sometime next year.

[jondoeuk]

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

[jondoeuk]

New preclinical data (Noile-Immune Bio's PRIME tech) https://mct.aacrjournals.org/content/early/2021/10/21/1535-7163.MCT-21-0400

[jondoeuk]

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

[jondoeuk]

The poster https://d1io3yog0oux5.cloudfront.net/_c4a3fd9db12be7ae245032a7178a2642/adaptimmune/db/249/3306/pdf/Hong+ESMO+2021+SURPASS+poster_UPLOADED2.pdf

[The Night Stalker]

STRANGE POS

[jondoeuk]

Here is the video

[jondoeuk]

Another slide

[jondoeuk]

Slides https://d1io3yog0oux5.cloudfront.net/_e7896ea0f6acb98530236acf35bbf90e/adaptimmune/db/249/3289/pdf/Final+ESMO+Adaptimmune+Company+Presentation.pdf

Video

[jondoeuk]

New PR https://www.globenewswire.com/news-release/2021/09/13/2295608/35803/en/Adaptimmune-Announces-Clinical-Responses-across-Five-Solid-Tumor-Indications-with-an-Overall-Response-Rate-of-36-and-Promising-Early-Durability-from-its-Next-Generation-SURPASS-Tri.html

[jondoeuk]

It seems that SURPASS-2 has now opened to recruitment in Spain https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-005802-24/ES

[jondoeuk]

''Next week, we will post the replay of the virtual update about our allogeneic programs. During the update, we shared our allo pipeline & the news that we we intend to file an IND for our first allo TCR against MAGE-A4 in late 2023. Click on the image to find the presentation.''

Next week, we will post the replay of the virtual update about our allogeneic programs. During the update, we shared our allo pipeline & the news that we we intend to file an IND for our first allo TCR against MAGE‑A4 in late 2023. Click on the image to find the presentation.

— Adaptimmune (@Adaptimmune) September 10, 2021

[jondoeuk]

Slides from an event (I will try and find the video) https://d1io3yog0oux5.cloudfront.net/_6c9fb7fbd463e9c5359539e13fc531b3/adaptimmune/db/249/3288/pdf/FINAL+presentation_Allo_08Sep2021.pdf

[kingclever]

This is hitting the radar on many platforms

[The Night Stalker]

bullish

[The Night Stalker]

bullish

[jondoeuk]

I agree, and the affirmation of the tech along with management from a company such as them reflects the real long-term value.

[Biggeoff]

carl icahn is taking a stake this week sometime

[The Night Stalker]

im invested at ELYS at moment

[The Night Stalker]

beauty

[The Night Stalker]

https://www.stockscores.com/chart.asp?TickerSymbol=%20adap&TimeRange=365&Interval=w&Volume=1&ChartType=CandleStick&Stockscores=1&ChartWidth=1100&ChartHeight=480&LogScale=None&Band=None&avgType1=SMA&movAvg1=50&avgType2=SMA&movAvg2=100&Indicator1=AccDist&Indicator2=StochRSI&Indicator3=CMF&Indicator4=MACD&endDate=&CompareWith=&entryPrice=&stopLossPrice=&candles=redgreen

[jondoeuk]

The collaboration has two components, development of allogeneic T-cell therapies for up to five shared targets and development of novel personalised allogeneic T-cell therapies. For each component, ADAP will be responsible for developing clinical candidates using its iPSC-derived platform to produce T-cells. Genentech will be responsible for the input of TCRs and subsequent clinical development and commercialisation.

ADAP will receive $150M upfront, the same amount over the next five years in additional payments, and development, regulatory and commercial milestones payments potentially exceeding $3B, as well as royalties (mid-single to low-double digits), across multiple programs.

https://www.globenewswire.com/news-release/2021/09/07/2292303/35803/en/Adaptimmune-Enters-into-a-Strategic-Collaboration-with-Genentech-to-Research-Develop-and-Commercialize-Cancer-targeted-Allogeneic-T-cell-Therapies.html

[jondoeuk]

Armed with these encouraging preliminary data, and with more data on the way, Adaptimmune is gearing up for its first regulatory filing for afami-cel as a treatment for advanced synovial sarcoma in 2022.

SPEARHEAD-1 full data will be at CTOS.

Meanwhile, the biotech also has plans to expand into several additional solid tumor types, such as liver, lung, and head and neck cancers.

A second registration-directed PhII (in esophageal or esophagogastric junction) will open soon and trials are already ongoing in HCC (data at ILCA), lung and H&N (data at ESMO)

[jaxstraw]

I'm guessing the Motley Fool and Yahoo articles.

[Watts Watt]

Has anyone discerned the reason for the recent jump from 3.96 to 4.34?

[Watts Watt]

From Motley Fool on June 21, 2021:

https://www.msn.com/en-us/money/topstocks/2-biotech-penny-stocks-that-are-vastly-superior-investments-to-dogecoin/ar-AALh8Ny?ocid=BingNewsSearch

Adaptimmune: The cutting edge of cancer care
While adoptive T-cell therapies have transformed the treatment paradigm for several types of liquid tumors, their utility in the solid tumor setting has so far been underwhelming. Adaptimmune, a small-cap immuntherapy company, is hoping to reverse this unfortunate situation with its SPEAR (Specific Peptide Enhanced Affinity Receptor) platform.


Last month, the company took a major step toward achieving this lofty goal by releasing mid-stage trial data for its lead product candidate known as afamitresgene autoleucel, or afami-cel for short. The main headline from this top-line data release is that afami-cel reportedly shrank tumors in a respectable 41.4% of heavily pre-treated patients with synovial sarcoma, a relatively uncommon type of soft tissue cancer.

Armed with these encouraging preliminary data, and with more data on the way, Adaptimmune is gearing up for its first regulatory filing for afami-cel as a treatment for advanced synovial sarcoma in 2022. Meanwhile, the biotech also has plans to expand into several additional solid tumor types, such as liver, lung, and head and neck cancers.

Why is Adaptimmune an intriguing growth play? First and foremost, the company's current market cap of $614 million pales in comparison to the value of its solid tumor pipeline as a whole. The market, in effect, is giving the company next to no chance at grabbing more than one minor indication within the next three years, despite these stellar top-line data in synovial sarcoma.

Secondly, the market is arguably undervaluing Adaptimmune's prospects as a buyout candidate. Big pharma could become keenly interested in the biotech's novel platform if afami-cel gets a green light from the Food and Drug Administration (FDA) next year.

Adaptimmune probably shouldn't be in penny-stock territory based on the steady progress of its unique cancer pipeline. So while patience may be required with this unloved biotech stock, Adaptimmune clearly ticks several boxes prized by value and growth investors alike.