Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
DTIL why weak after strong report today?
PR https://www.biospace.com/article/releases/precision-biosciences-provides-update-on-allogeneic-car-t-programs-and-path-forward-with-its-lead-pbcar0191-candidate-for-car-t-relapsed-patient-population/
Slides https://investor.precisionbiosciences.com/static-files/717d82d7-d304-4428-ba22-1a19c965d8d5
The most popular first salvage regimen for relapse or progression was an alternate CAR-T therapy (dual or alternate target) regardless of CD19 positivity. 27% of responders chose this regimen for CD19 positive relapse, while 31% of responders did so for CD19 negative relapse. 88.5% of responders favored consolidative allogeneic hematopoietic cell transplantation (alloHCT) after response to salvage, whereas 51.2% of physicians would consider autologous hematopoietic cell transplant (AHCT) in transplant naïve patients.
https://www.astctjournal.org/article/S2666-6367(22)01360-4/fulltext#.Yp5U3ghW7h4.twitter
Targeting PARP11 to avert immunosuppression and improve CAR T therapy in solid tumors
From memory, the ORR for PBCAR0191 plus eLD chemo was 100% (66% CR rate) and the response duration exceeded the original response to an auto product in three of five. If it holds up in a larger population a registration-directed PhII could happen.
There is also clinical data from patients with R/R DLBCL and R/R CLL, which shows a correlation with (durable) responses and the proportion of naïve and/or memory-like CD8+ T-cells.
Hopefully, the optimised manufacturing process (which the company has talked about) for PBCAR19B has allowed them to increase the phenotype(s) without the need for a new IND application.
As for the strategies outlined in that (and other papers) for increasing efficacy will be looked at by them as they could easily be incorporated into future trials.
Response MCL AUTO limited by:
1. T cells fitness and dose of CD8 and CCR71 CD45RA1 T cells too low.
2. High TB
P2 trial of the autologous anti-CD19 chimeric antigen receptor (CAR)
T-cell therapy brexucabtagene autoleucel (KTE-X19) in patients with heavily pretreated MCL. The median DOR was 46.7 months among patients with CR (46/71) and 2.2 months in patients with PR (16/71)
https://ashpublications.org/bloodadvances/article/4/19/4898/464200/Tumor-burden-inflammation-and-product-attributes
phase II trial of the autologous anti-CD19 chimeric antigen receptor (CAR)
T-cell therapy brexucabtagene autoleucel (KTE-X19) in patients with heavily pretreated MCL
The median DOR was 46.7 months among patients with CR (46/71) and 2.2 months in patients with PR (16/71)
https://ascopubs.org/doi/pdf/10.1200/JCO.21.02370#.YptkxkBhQis.twitter
“The CAR T relapse setting is a rapidly growing area with dire unmet medical need that is not adequately addressed by current treatment options.”
https://ascopubs.org/doi/full/10.1200/JCO.21.02370
These pharma execs didn't want to talk about allo. DTIL has shown T cells from a healthy donor beat exhausted T cells from the lymphoma pts. who relapsed on auto. Increasing the dose from 300 to 500 M should result in high CR @ 28 days.
For auto. Here is (AUTL's) Dr. Pule on so-called point-of-care
The company will share an update on its CAR-T programs during a company-hosted webcast and conference call on the 8th at 8:00 AM ET.
Efficient reprogramming of T cells with a CAR in as little as 24 hours in a more simplified manufacturing process without T cell activation or extensive culture outside the body also offers the possibility of expanding where and when these therapies are produced
https://www.pennmedicine.org/news/news-releases/2022/march/penn-researchers-shorten-manufacturing-time-for-car-t-cell-therapy
Longterm potential maybe? Good price to get in now? Could see how this could go up exponentially?
Donor T cells and donor genes to treat cancers?
Delivery of twin (AAV) capsids carrying 2 payloads: one with the nuclease to cut genomic DNA at the well-characterized PCSK9 locus and the other with a therapeutic donor gene, providing a potential path to permanent expression of a healthy gene
The long-term risks of off-target editing are unclear although
we are encouraged by the over 42 years of event free followup in 33 NHPs we have studied with this nuclease
I think you mentioned B2M going back. I know one group made a recombinant adenovirus carrying the gene and demonstrated recovery of HLA-I expression on cancer cells deficient in that. This lead to destruction by CD8+ T-cells https://onlinelibrary.wiley.com/doi/10.1111/j.1365-3083.2009.02276.x https://www.nature.com/articles/cgt201432
So that is one way. As for Tregs, ''In mice and humans, CCR8+ Tregs constituted 30 to 80% of tumor Tregs in various cancers and less than 10% of Tregs in other tissues, whereas most tumor-infiltrating conventional T cells (Tconvs) were CCR8–. CCR8+ tumor Tregs were highly differentiated and functionally stable.'' https://www.pnas.org/doi/10.1073/pnas.2114282119
The reason I mention that is due to a few anti-CCR8 mAbs in the clinic. So are anti-CD25 and anti-GARP mAbs https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116816/ https://aacrjournals.org/cancerres/article/81/13_Supplement/1847/667728/Abstract-1847-Anti-GARP-antibody-DS-1055a-augments
I do think CAR-T's will have a role in treating solid tumours, but they will need to do more to overcome the hurdles that exist, such as immunosuppressive TMEs. I know they were working on shRNA to knockdown different genes, so expand that and look to incorporate a cassette to target a number.
Sounds like the second for up to five antigens. They haven't disclosed them or how Genentech identified the TCRs.
How about inserting MMR gene into MSI cancers and knock out gene expressing IL-1R1?
Hutch researchers scanned specimens representing 21 different cancer types. Looking only for the gene encoding the rarer IL-1R1 protein, they saw it pop up, at varying levels, among all 19 solid-tumor cancer types.
If DTIL can unsteath cancer cells before treating pts with stealth T cells from donors, ORR will be a lot higher. No need for neoantigens
ADXS called that HOT. It turned out to be ice as neoantigens are like fingerprints
It is ''personalised'' in a sense. ADAP will be responsible for developing clinical candidates using its iPSC platform, while Genentech responsible for the input of patient-specific neoantigen-reactive TCRs and subsequent clinical development and commercialisation.
Is 'personalized allogeneic' oxymoron?
I do think they should focus on their so-called stealth cells, so by the end of the year look to stop the PBCAR019 trial and focus on PBCAR019B. They also have another four targets https://www.businesswire.com/news/home/20210415005982/en/Precision-BioSciences-Reacquires-Global-Rights-to-its-Allogeneic-CAR-T-Programs
So make an assessment of them and maybe look to move PBCAR371A* into the clinic.
* An anti-CLL-1 CAR-T
I agree. RHHBY's Genentech signed a deal with ADAP 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
Both are iPSC-derived, but the most interesting is the personalised therapy (targeting neoantigens) they are working on together.
Cell therapy will be the backbone of therapies to treat solid tumors.
Roche is testing a mechanism that blocks TIGIT, a receptor capable of shrouding cancer cells from the immune system. Its drug, tiragolumab, binds to the receptor, preventing its deception. Roche added the new drug to its blockbuster medicine Tecentriq in patients with a form of lung cancer.
But during an interim analysis, Roche's regimen failed to meet the study's two key goals. It didn't have a statistically significant impact on the length of time before patients worsened — a measure known as progression-free survival. And it didn't improve overall survival.
https://www.investors.com/news/technology/biotech-stocks-arcus-and-others-hammered-on-roche-flop-in-lung-cancer/?src=A00220
NVS should buy DTIL with their stockpile of peanuts.
New YTB323 data https://library.ehaweb.org/eha/2022/eha2022-congress/357076/michael.dickinson.phase.i.study.of.ytb323.a.chimeric.antigen.receptor.28car29-t.html
Also, PHE885 https://library.ehaweb.org/eha/2022/eha2022-congress/358303/adam.s.sperling.phase.i.study.data.update.of.phe885.a.fully.human.html
NVS claimed to deliver 10-50 fold few CART T cells. That means they can find 2 mil. non exhausted T cells and turn them into CART T in 2 days from the patient's blood draw. DTIL may be doing the same using their optimized process with the blood from health donors.
The target YESCARTA dose is 2 × 106 CAR-positive viable T cells per kg body weight, with a maximum of 2 × 108 CAR-positive viable T cells.
Is NVS picking CD39-CD69- t cells? Which alloc CART T in clinical trial is CD39-CD69-?
Hi NY1972, ARCUS is superior in soooo many ways. Precision Biosciences is the winner in the long term.
I will never get why Wallstreet sometimes buries the best and elevates the rest. Don’t get me wrong the advanced programs of CRSP, INTL and ALLO deserve credit, but the risks are high. Higher than DTIL. That is for ding dong sure.
Ticking time bomb? monitoring patients undergoing CRISPR-Cas9-based editing for clinical therapeutics for pre-existing p53 and KRAS mutations
https://www.nature.com/articles/s41467-021-26788-6
Too many biotechs were fat pigs destined for slaughter. DTIL is actually 2 bios. $1 for allo CART T, $1 for ARCUS.
T-charge must be a magical hotel for the wandering TILs.
Nothing I could fine. Q1 financials are on Monday.
If LD conditioning is part of the treatment, NVS should have 5-7 days to grow AUTO CART T, not 2 days.
https://ash.confex.com/ash/2021/webprogram/Paper146268.html
No, but it is used. Either fludarabine (30 mg/m2 daily for three days) plus cyclophosamide (500 mg/m2 daily for three days), or bendamustine (90 mg/m2 daily for two days).
No LD mentioned in YTB323 P1 protocol
https://clinicaltrials.gov/ct2/show/NCT03960840?term=YTB323&draw=2&rank=1
YTB323 (anti-CD19) is being tested in patients with DLBCL or CLL/SLL. For CLL/SLL in order to be potentially eligible, SD or PR after at least six months of ibrutinib, either as a second or subsequent line of therapy. As for DLBCL, relapsed or refractory after two or more lines of therapy, including auto stem cell transplant. Also, no prior CD19-directed therapy. It is given after LD chemo.
PBCAR0191 with eLD will be targeting AUTO CART relapsed pts. Stealth cells + CD3 mAb with LD will be their next gen offering for 2024.
CART T as 1st line treatment without LD?
Novartis said it used T-Charge, a new CAR-T manufacturing platform, to reduce the incubation time in vitro to 24 hours and the completion of the product to less than two days. With T-Charge, CAR-T cell expansion occurs primarily within the patient’s body (in-vivo), eliminating the need for an extended culture time outside of the body (ex-vivo)
http://www.koreabiomed.com/news/articleView.html?idxno=12767
Based on the data so far, PBCAR0191 with eLD seems to be on par with auto CAR T's. In NHL (n=17), the ORR was 71%, with a CR rate of 53%. In B-ALL (n=5), the ORR was 80%, with a CR rate of 80%. However, durability needs to improve.
Clinical data https://www.globenewswire.com/news-release/2021/12/13/2351117/0/en/Novartis-announces-T-Charge-next-generation-CAR-T-platform-with-first-in-human-data-at-ASH-2021.html
Focusing on auto doesn't make a huge amount of sense long-term.
NVS CART T needs a charge soon. Selling a salvage therapy seems to be the only viable option near term.
YTB323, an investigational, autologous CD19-directed CAR-T cell therapy developed using the T-Charge platform, showed promising results in the diffuse large B-cell lymphoma arm of a first-in-human, multicenter, Phase I dose-escalation study. Patients received a single treatment of YTB323 at two dose levels (DL). The median administered doses were 2.5×106 CAR+ cells (DL1; n=4)
Followers
|
23
|
Posters
|
|
Posts (Today)
|
0
|
Posts (Total)
|
301
|
Created
|
12/13/19
|
Type
|
Free
|
Moderators |
Volume | |
Day Range: | |
Bid Price | |
Ask Price | |
Last Trade Time: |