Precision BioSciences Inc (DTIL)

[Monksdream]

DTIL new 52 week low

[Monksdream]

DTIL new 52 wewek low

[NY1972]

DTIL founders never worried about cash until the meltdown. They hired too many PhDs, built fancy expensive labs with lots of promises. They never tried to trim the expenses to make sure there will be cash left for clinical trials. High burn and lots of GT bios spell doom for this bio.

[jondoeuk]

I should have pointed out that companies are happening to develop small[er] nucleases. Here is one paper from Casebia Therapeutics, which is a joint venture between CRSP and BAYN https://www.nature.com/articles/s41467-021-24454-5

Also, in 2020, researchers led by Dr. Liu created a new base editor that could perform C-to-T conversion of DNA in mitochondria. However, it had limitations, not only being restricted to that conversion, but mostly limited a certain motif. This means that it could correct only 10% of confirmed pathogenic mitochondrial point mutations https://www.nature.com/articles/s41587-022-01256-8

Last year another novel base editor was created that could achieve A-to-G conversion. Being able to perform that could correct 43% of confirmed pathogenic mitochondrial point mutations https://www.cell.com/cell/fulltext/S0092-8674(22)00389-0

However, I don't see either base editor entering the clinic for a number of years.

[jondoeuk]

Or it could end up like TRIL. ARCUS has some benefits over current CRISPR systems, manly its size, can edit the mitochondrial genome and IP is not a mess.

[NY1972]

IECure will buy the ARCUS IP when cash is 0 in 18 months.

[jondoeuk]

Not the most productive use of its cash so far. The R&D Day could change that, but the market doesn't seem to think it.

[NY1972]

this is a homeless shelter for PhDs. Cash is not spent on patients. They hired a chief people officer to cut the pie.

[jondoeuk]

The market did not find the recent announcement attractive https://www.businesswire.com/news/home/20230815091930/en/Precision-BioSciences-Completes-Strategic-Transaction-with-Imugene-for-Azer-Cel-in-Cancer

I think a reverse split is a possibility, especially after the announcement couldn't move the PPS. If that happens, will likely add fuel to any downward price pressure. Management don't seem the best. Now it's do or die with the in vivo programs.

[rtrstock]

That's what I'm afraid of, guess I'll just wait. Keep my shares.

[J-mak]

In my opinon slim very very slim

[rtrstock]

What's the educated guess?

What's realistically possible by October date for pps to be more than $1.00

[J-mak]

Didn't you already say that

[Monksdream]

DTIL new 52 week low

[rtrstock]

$227 Million in Upfront Economics and Milestone Payments for Azer-Cel in Addition to Double-Digit Royalties on Sales
Imugene
https://www.businesswire.com/news/home/20230815091930/en/Precision-BioSciences-Completes-Strategic-Transaction-with-Imugene-for-Azer-Cel-in-Cancer

[Monksdream]

DTIL new 52 week low

[rtrstock]

Well I hope sofmething works out, I'm all in on this one , and have been steadily accumulating shares.
If I recall correctly, Moderna pps was high for years before they ever had an approval for a product.
I see so much potential for this company I'm putting everything I have on it. Will see what happens.

[jondoeuk]

Notice of delisting was on the 28th of April. This gives them a 180-day period to regain compliance ($1.00 for a minimum of ten consecutive business days). If not, they could file for an extension.

[jondoeuk]

It would be interesting to see what a partnership could look like for azer-cel and/or PBCAR19B. A strategic sale? They mention they will focus on in vivo therapies multiple times, which says it all! https://finance.yahoo.com/news/precision-biosciences-provides-updates-azer-113000560.html

[rtrstock]

Hope this doesn't delist?
What is possible right now?

[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