Precision BioSciences Inc (DTIL)

[jondoeuk]

The poster https://tunetx.com/wp-content/uploads/2023/05/TuneTx-ASGCT-2023_CAR-T.pdf

[jondoeuk]

PR https://www.businesswire.com/news/home/20230531005625/en/Precision-BioSciences-Provides-Update-on-Allogeneic-CAR-T-Programs-and-Regulatory-Path-Forward

Slides https://investor.precisionbiosciences.com/static-files/df1179ae-c2c7-4f88-bb3e-431293fa6ba6

[swampboots]

DTIL .77 and this this morning:
Precision BioSciences to meet with FDA after touting allogeneic CAR-T win

https://endpts.com/precision-biosciences-to-meet-with-fda-after-touting-allogeneic-car-t-win/


But market6 does not think they will not need too much cash before gems show?

[jondoeuk]

From FB https://www.fiercebiotech.com/research/precision-biosciences-boasts-preclinical-data-two-gene-editing-programs-making-its-case

[jondoeuk]

The company will provide an update on its CAR-T programs via a hosted virtual webcast and conference call on the 31st at 8:30 AM ET https://edge.media-server.com/mmc/p/2r6qgv6c

[jondoeuk]

This was presented (CAR-T) https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=13716

[jondoeuk]

Two LBAs (at ASGCT)

One from Tune https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=15223

Another from Precision https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=15227

[jondoeuk]

It could. Another might be the direction the company had taken. Looking at how much they have burnt through, there is not much to show for it clinically. As for the (ASGCT) abstract, preclinical and clinical data from other groups is conflicting, with some suggesting that KO might negatively affect expansion, persistence and/or function.

[NY1972]

Here is 1 reason why CSO left. Looks like ALLO is a bunch of born losers.
agct presentation from Novartis showing KO of endogenous TCR is deleterious to CAR-T function [269]; corroborates some academic work that was released previously

[NY1972]

PhDs love stock options from new bios. The bio bucks from retail investors made them muti-millionaires.

[jondoeuk]

Some of the authors have links to Tune Therapeutics https://www.biorxiv.org/content/10.1101/2023.05.01.538906v1

[NY1972]

Too many high paid spoiled PhDs. Too much CART competition. Bios can no longer print money. Many already died. Many will

[rtrstock]

What is the future of the company?


I'm just hoping this doesn't reverse split.

[jondoeuk]

He has now taken up the same position at Tune Therapeutics, which is not far from where this company is located. Matt Kane (another founder of DTIL) is the CEO.

As for antigen downregulation, that is one mechanism of resistance. Antigen loss (up to 30% of B-cell ALL patients who initially respond can relapse with a CD19 negative clone(s)), truncated protein, or downregulation, loss or mutation of CD58 are others https://www.jci.org/articles/view/159402

Long-term (assuming positive clinical data this year), want 19B to displace 2nd/3rd-line auto, but other companies are already working on ways to overcome those and other mechanisms of resistance. So, I think they should be doing the same, including creating an anti-CD19/CD20 CAR https://aacrjournals.org/cancerimmunolres/article/4/6/498/468518/T-Cells-Expressing-CD19-CD20-Bispecific-Chimeric https://ashpublications.org/blood/article/136/Supplement%201/53/470303/CD58-Aberrations-Limit-Durable-Responses-to-CD19 https://www.abstractsonline.com/pp8/#!/10828/presentation/3056

[NY1972]

CSO left. Worse significant antigen expression decrease after CAR T-cell therapy
https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.14910

[jondoeuk]

Could be. Even if not, every time the company misses dates that they have committed to, lose credibility, and doesn't give one confidence either. As for toxicities, are switching to a sLD regime (over enhanced), so that should help. In terms of T-cells, at least there are data suggesting the new manufacturing could help.

[NY1972]

It will be delayed in May. CART is too toxic for CART relapsed pts.

[jondoeuk]

The update is now expected in May.

[jondoeuk]

This is recent https://www.nature.com/articles/s41586-023-05787-1

[NY1972]

Have you seen any tumor biopsy studies comparing T cell counts baseline and post atezolizumab IV or other PD1 mAbs?

[jondoeuk]

So far, they have overpromised and under-delivered.

As for safety, I know they looked at product characteristics and showed Grade >3 ICANS correlated strongly with the effective stem central memory phenotype CD4+ T-cell dose, differentiated CD4+CCR7- T-cell dose and CD4:CD8 ratio. In addition, other factors, such as tumour burden and Cmax of IL-6, IL-2 and IP10 did. Interestingly, IL-6 plays a role in CRS (S)AEs https://ashpublications.org/blood/article/130/21/2295/36661/Kinetics-and-biomarkers-of-severe-cytokine-release

The new manufacturing protocol was intended to maximise the stem central memory phenotype T-cell fraction (CCR7+), while limiting the CD4+ CCR7- differentiated fraction, that could improve the safety and efficacy of the product. Looking at the poster, the median, desired memory T-cell proportion from Process 1.0 to 1.1b increased from 52.75% to 75.00%. Median healthy cells proportion from Process 1.0 to 1.1b increased from 15.67% to 43.20%, and CD4:8 range decreased from 25.16% to 2.47%.

[NY1972]

19A, B kept alive so many PhDs can draw a paycheck. 4/4 CR for CART relapsed pts. in AFM13 MDACC trial. No CRS, death....NK is the future IMO

[jondoeuk]

Now they are promising to give an update on azer-cel "once sufficient follow-up supports meeting FDA to discuss clinical plans,'' so April or May. So much for Q1! As for 19B, that April or May update will include data from DL2, with ''expectation of durability data to follow this year."

[carusso]

What does anyone think of the annual report?

[NY1972]

The update will be under the rug.

[jondoeuk]

I hope the CAR-T update won't be a few sentences in a PR!

[jondoeuk]

PR https://www.businesswire.com/news/home/20221210005005/en/Precision-BioSciences-Presents-Analysis-of-Azer-Cel-Allogeneic-CAR-T-Product-Attributes-Related-to-In-Vivo-Pharmacokinetics-Pharmacodynamics-and-Clinical-Outcomes-at-2022-American-Society-of-Hematology-Annual-Meeting

Poster https://precisionbiosciences.com/wp-content/uploads/2022/12/ASH-2022_poster_vF.pdf

[rtrstock]

Precision Biosciences announces change to Board of Directors
https://www.businesswire.com/news/home/20221110006055/en/Precision-BioSciences-Announces-Change-to-its-Board-of-Directors

[jondoeuk]

ASH abstract

2005 Effective Cell Dose and Functional Attributes of Azercabtagene Zapreleucel (azer-cel; PBCAR0191) Associate with Allogeneic CAR T-Cell Safety and Efficacy in Patients with Relapsed/Refractory B-Cell Lymphoma https://ash.confex.com/ash/2022/webprogram/Paper165311.html

[rtrstock]

CART-T white blood cell treatment, experimental, girl cured of Lukemia, 10 years have gone by, 0 cancer cells, not Precision, however this is why I'm continuing to add to this investment, remarkable potential.

Dr. Siddhartha Mukherjee, a leading cancer specialist and researcher at Columbia University in New York, and the Pulitzer Prize-winning author of "The Emperor of All Maladies: A Biography of Cancer

https://www.msn.com/en-us/health/health-news/how-an-experimental-treatment-beat-a-little-girls-cancer/ar-AA13xJoA?ocid=hplocalnews&li=BBnb7Kz

[rtrstock]

Cathie Martin, has gained an approval for Purple Tomatoes in the U.S., antioxidant rich. She's apparently a brilliant genetic scientist with Norfolk Plant Scientists, now I know Precision Biosciences has billions in funding from Cargill, in consideration of plant genetics, I'd love to see a collaboration benefiting all. Congratulations to Cathie and her team, an excellent U.S.D.A. Approval, tomatoes expected to be distributed as early as 2023.

https://www.msn.com/en-us/foodanddrink/foodnews/usda-approves-genetically-modified-antioxidant-rich-purple-tomato/ar-AA12mnNy?li=BBnb2gh

[swampboots]

DTIL: (1.50's or lower target buying price) I am a sometimes investor as stock uses its shareholders to sponsor its expensive goals, But recent multiple handshakes with top tiered drug houses, insider buying, and recent share offering swallowed into current share price offered (to me) better safety than peers which lacked such a recent trifecta.
Highly notable to me and more comforting as an investor are the almost daily discoveries of new mechanisms which may introduce new solutions that for example may block or turn on or off influences which affect even approved CART-T safety and effectiveness. In my opinion, this implies that all Cart-T platforms have available outsource able safety nets to in theory most likely improve their platform in a significant profitable way, and made available to patients as long as the cost of their treatment has a market for their improved delivery system.
https://medicalxpress.com/news/2022-09-immune-cells-cancer.html?utm_source=
https://www.sciencedaily.com/releases/2022/09/220909191820.htm


(if a problem with the links) a copy and paste on Goggle did the trick for me.

[jondoeuk]

New preclinical data https://www.nature.com/articles/s41417-022-00518-6

[jondoeuk]

(OT) Two new papers https://medicalxpress.com/news/2022-08-technology-success-car-t-cell-immunotherapy.html https://www.businesswire.com/news/home/20220828005032/en/New-Data-in-Nature-Medicine-Suggest-Pre-Treatment-Tumor-Microenvironment-Can-Impact-Response-for-CAR-T-Cell-Therapy-in-Patients-with-Large-B-Cell-Lymphoma

[jondoeuk]

The company's long-term goal is for PBCAR19B to displace auto products. The program was strategically paused in Q1 to implement an optimised manufacturing process, which was to increase a T-cell memory subset with stem cell-like properties. Data on some patients treated at DL2 (540M cells) with the new lots, as well as those from DL1 (270M cells) could either be presented at ASH or an investor event. However, it won't be until next year until there will be a longer follow-up for durability. So until then we won't have an idea if it really could do what they hope.

Moving to PBCAR269A with nirogacestat, I have mixed views about this program. I know the CAR can't target cells with low BCMA levels (which is why they added niro). Also, the space is becoming more crowed, and many are moving toward dual targeted CARs. If they would do the same, but target other antigens that aren't being pursued by many, that could be a better long-term strategy.

[jondoeuk]

Thanks for the list. It is not long compared to the one for CD19.

No, but in the trial, patients receive two cycles of LD chemo, followed by AFM13 pre-complexed cbNKs and three weekly IV infusions of AFM13, so slightly more involved than CAR-T.

I am trying to figure out how innate engagers affect TAMs thru CD16.

The innate cell engagers bind to the CD16a receptor on NK cells and macrophages https://www.tandfonline.com/doi/full/10.1080/19420862.2019.1616506 https://www.sciencedirect.com/science/article/pii/S0006497119371605

Also, for a number of the trials they are adding either an anti-PD(L)-1 or pre-complexed cbNKs as well.

[swampboots]

I think it is an interesting attempt to place DTIL's CART-T platform in comparison to its "peers".
but a highly impossible task without sorting out the 1000's of new studies each month in this field. I am relying on insider buying, fruitful handshakes with some big drug Companies, the Co's cash burn position, as well as the shortness of time since last pipe dilution.
With no scientific credentials I read dozens of new studies a day in the cancer field, and
try to imitate a journalist in my digestions of the information relayed as tidy summaries.
And weekly for sure new tweaks to the Cart-T arena are proposed, some to reduce costs, improve accuracy, limit mis-maufacturing mistakes in the expensive customizing of their applications, as microscopic contamination difficult to contain or measure.. In addition to toying with new discovered proteins which must be suppressed, added or mingled to make the CART-T platform more effective. It is a moving target where one simple new discovery can weigh heavily on the ultimate effectiveness toward endpoint mastery.......To repeat I have to assume insiders and big drug Co.'s offering some of their risk , favors the odds to me by relying on better eyes concluding more probable credibility, as their surveilance is closer to the microscope sorting out the unresolved challenges I am not in the loop to know..

[NY1972]

Thanks for the list. It is not long compared to the one for CD19. I am trying to figure out how innate engagers affect TAMs thru CD16.

[jondoeuk]

It faces competition from other cell therapies. I know TT11 (an auto anti-CD30 CAR-T) is already in a pivotal trial for late stage cHL [1], late stage CD30+ NHL, as well as a potential second line therapy (plus four doses of Opdivo) in cHL.

TT11X (healthy donor EBVSTs, with the same CAR) is also being tested in CD30+ lymphomas [2]. NTLA is also moving forward a healthy donor anti-CD30 CAR-T [3]. Another potential benefit is addition engineering. In this, they added a chemokine receptor [4].

Refs:
1 https://www.globenewswire.com/en/news-release/2021/12/13/2351226/0/en/Tessa-Therapeutics-Announces-Positive-Data-from-Phase-2-Trial-of-Autologous-CD30-CAR-T-Therapy-TT11-in-Relapsed-or-Refractory-Classical-Hodgkin-Lymphoma-at-2021-ASH-Annual-Meeting.html
2 https://www.globenewswire.com/en/news-release/2021/12/11/2350320/0/en/Tessa-Therapeutics-Showcases-Positive-Clinical-Data-from-Phase-1-Study-of-Off-the-Shelf-CD30-Cell-Therapy-at-2021-Annual-Meeting-of-American-Society-of-Hematology-ASH.html
3 https://www.globenewswire.com/en/news-release/2022/05/02/2433370/0/en/Intellia-Therapeutics-Presents-Preclinical-Data-Demonstrating-Advancements-in-its-CRISPR-Engineered-Allogeneic-Platform-at-the-2022-Keystone-Symposia-s-Precision-Genome-Engineering.html
4 https://ashpublications.org/blood/article/138/Supplement%201/742/480022/CD30-Directed-CAR-T-Cells-Co-Expressing-CCR4-in

[carusso]

New to this board. Could anyone tell me the main reasons for the decline in share price here since last Sept/Oct highs?

[NY1972]

cbNK cells pre-complexed with engager is safe and CAR like.

As of October 31, 2021, a total of 18 patients with CD30-positive relapsed or refractory Hodgkin and non-Hodgkin lymphomas (16 and 2 patients, respectively) were treated with the novel combination of cbNK cells pre-complexed with AFM13.
As of the cutoff date, 16 of 18 patients had achieved an objective response to the treatment according to investigator assessment, with seven complete responses (CR) and nine partial responses.
100% objective response rate (ORR) was observed with a 42% CR rate in 12 patients with Hodgkin Lymphoma, after the 1st of 2 planned cycles at the recommended phase 2 dose of 108 cbNK cells/kg pre-complexed with AFM13.
No cases of serious adverse events such as cytokine release syndrome, neurotoxicity syndrome or graft-versus-host disease were observed.
Treatment was well tolerated with five reported cases of transient infusion related reactions after the monotherapy infusions of AFM13.

[jondoeuk]

The poster is now up https://precisionbiosciences.com/wp-content/uploads/2022/07/Pires-M-Allogeneic-CAR-T-Cells-with-Deoxycytidine-Kinase-Knockdown.-SITC.-2021..pdf

Others, include knockdown of CD319 (reduces or prevents fratricide of CAR+ cells), TGFRB2 (less susceptible to immunosuppression by transforming growth factor beta), CBL-B (less susceptible to suppression of TCR and PD-L1 signaling), CD52 (less susceptible to CD52 antibody induced death) and/or the glucocorticoid receptor (less susceptible to glucocorticoids).

Hopefully, they will start to incorporate these and build a 'library' of additional shRNAs targeting more genes, such as PD-1 https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(21)00498-6 https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.7522 https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.e14514

[swampboots]

DTIL 2.15 -1.61 I am all ears.

[rtrstock]

https://www.defenseworld.net/2022/08/15/sg-americas-securities-llc-buys-shares-of-10821-precision-biosciences-inc-nasdaqdtil.html

Hedge Funds and other institutional investors buying Precision Biosciences stock.

[rtrstock]

Can't believe there isn't more talk on InvestorsHub about Precision Biosciences after Friday, +23% hope this continues up, I really need it.

[swampboots]

Just put sickle cell drug into google search and mystery will be solved, and if you are displeased with me pumping DTIL all along, I want to know about it!.

[carusso]

And what is YOUR first language?

Such interesting people here...

[swampboots]

DTIL 1.90 as mist of sickle cell throw by a big boy drug house, of billions into
some platform drug.

[swampboots]

DTIL Goldman Sachs lowers target to $2, I need below 1.50 to restart safe.

[swampboots]

DTIL sold all into .45 loss as expected (above 1.70's) , but boring wait till data, so want lower to get back all I sold.