Allogene Therapeutics (ALLO)

[Monksdream]

ALLO new 52 week low

[NY1972]

Yes. Signet-ring, TP53. ... dying. Even more aggressive than the ones enrolled in CART trial

[jondoeuk]

Was that the case study (50-year-old female)?

I know the CAR-T is already in registrational trials both in China and the US. If all goes to plan, they expected to submit an NDA to the NMPA in 2024 and a BLA to the FDA in 2025. A next-gen version is in the clinic as well https://aacrjournals.org/clincancerres/article/26/20/5494/82735/Coexpression-of-IL7-and-CCL21-Increases-Efficacy

Also https://www.biospace.com/article/moderna-carsgen-join-forces-combining-mrna-cancer-vaccine-with-car-t/

However, it's getting pretty crowded

[NY1972]

$AFMD 24+ ATEZO was pretty effective (1/1) compared to CARThttps://t.co/WtuFoQNM37

— Bon Wood (@ny1972_47) September 28, 2023

[jondoeuk]

Upcoming https://www.globenewswire.com/news-release/2023/09/27/2750477/0/en/Allogene-Therapeutics-Announces-Three-Poster-Presentations-from-its-Next-Generation-AlloCAR-T-Platform-at-the-Society-for-Immunotherapy-of-Cancer-SITC-Annual-Meeting.html

[dmerc]

short 49% Mentioned by Roensche Capital

[dmerc]

https://www.benzinga.com/quote/ALLO/analyst-ratings

[jondoeuk]

An oral presentation at AACR next month https://www.abstractsonline.com/pp8/#!/10828/presentation/10251

[jondoeuk]

A proprietary approach to control rejection https://www.globenewswire.com/news-release/2022/11/10/2553356/0/en/Allogene-Therapeutics-Unveils-Novel-Approach-to-Generate-Engineered-AlloCAR-T-Cells-to-Control-Immune-Rejection-at-the-Annual-Meeting-of-the-Society-for-Immunotherapy-of-Cancer.html

This is one of a number of next-gen technologies being pioneered. Others, include https://www.globenewswire.com/en/news-release/2023/02/01/2599947/0/en/Allogene-Therapeutics-Presents-Data-on-Dagger-a-Next-Generation-AlloCAR-T-Platform-Technology.html

[jondoeuk]

R&D showcase PR https://www.globenewswire.com/news-release/2022/11/29/2564467/0/en/Allogene-Therapeutics-R-D-Showcase-Features-Hematologic-and-Solid-Tumor-Advances-Across-its-AlloCAR-T-Platform.html

Slides https://ir.allogene.com/static-files/3eacf8bf-3cd0-47bc-a5ac-f5715083883a

[jondoeuk]

ASGCT PR https://www.globenewswire.com/news-release/2022/05/19/2446950/0/en/Allogene-Therapeutics-Announces-Oral-Presentation-of-Pre-Clinical-Data-Highlighting-Improved-Anti-Tumor-Activity-of-Donor-Derived-Allogeneic-CAR-T-Cells-at-American-Society-of-Gene.html

[jondoeuk]

New preclinical data https://aacrjournals.org/cancerrescommun/article/2/3/158/684708/Allogeneic-Anti-BCMA-CAR-T-Cells-Are-Superior-to

[jondoeuk]

Additional data https://allogene.com/resources/download/ALPHA-Study.pdf https://allogene.com/resources/download/ALPHA2-Study.pdf https://allogene.com/resources/download/UNIVERSAL-Updated-Phase-1-Data-Validates-Feasibility-Allogeneic.pdf
https://ir.allogene.com/static-files/891ef05d-ff61-4c95-9a55-9ff7a515102d

[jondoeuk]

AS PR's https://www.globenewswire.com/news-release/2021/12/13/2350984/0/en/Allogene-Therapeutics-Reports-Positive-Results-from-Phase-1-UNIVERSAL-Study-of-Single-Dose-ALLO-715-AlloCAR-T-Cell-Therapy-in-Relapsed-Refractory-Multiple-Myeloma-at-the-63rd-Ameri.html

https://www.globenewswire.com/news-release/2021/12/13/2350962/0/en/Allogene-Therapeutics-Reports-Positive-Phase-1-Data-from-the-ALPHA-Trials-in-Non-Hodgkin-s-Lymphoma-at-the-63rd-Annual-Meeting-of-the-American-Society-of-Hematology.html

[jondoeuk]

Abstracts

ALPHA2 Study: ALLO-501A Allogeneic CAR T in LBCL, Updated Results Continue to Show Encouraging Safety and Efficacy with Consolidation Dosing https://ash.confex.com/ash/2021/webprogram/Paper146045.html

ALPHA Study: ALLO-501 Produced Deep and Durable Responses in Patients with Relapsed/Refractory Non-Hodgkin’s Lymphoma Comparable to Autologous CAR T https://ash.confex.com/ash/2021/webprogram/Paper146038.html

Universal Updated Phase 1 Data Validates the Feasibility of Allogeneic Anti-BCMA ALLO-715 Therapy for Relapsed/Refractory Multiple Myeloma https://ash.confex.com/ash/2021/webprogram/Paper145572.html

[jondoeuk]

ASH data https://www.globenewswire.com/news-release/2021/11/04/2327658/0/en/Allogene-Therapeutics-to-Showcase-Clinical-Data-from-the-ALPHA-ALPHA2-and-UNIVERSAL-AlloCAR-T-Trials-at-the-63rd-Annual-Meeting-of-the-American-Society-of-Hematology.html

[makinezmoney]

$ALLO: 2nd day of bouncing off bottom...... now $17.25



GO $ALLO

[jondoeuk]

New PR https://www.globenewswire.com/news-release/2021/06/04/2242102/0/en/Allogene-Therapeutics-Presents-Positive-Phase-1-Data-on-ALLO-501-and-ALLO-501A-in-Relapsed-Refractory-Non-Hodgkin-Lymphoma-at-the-2021-Annual-Meeting-of-the-American-Society-of-Cli.html

Posters https://www.allogene.com/resources/download/First-In-Human-Data-of-ALLO-501A.pdf https://www.allogene.com/resources/download/Safety-and-PK-PD-of-ALLO-647.pdf

[conix]

Allogene Therapeutics (NASDAQ:ALLO) was upgraded by analysts at Truist Securities from a "hold" rating to a "buy" rating. They now have a $41.00 price target on the stock, up previously from $34.00.This represents a 64.3% upside from the current price of $24.96.

[jondoeuk]

The PR https://www.globenewswire.com/news-release/2021/05/19/2232864/0/en/Allogene-Therapeutics-CD19-Forum-Highlights-Positive-Results-from-Phase-1-Studies-of-ALLO-501-and-ALLO-501A-in-Relapsed-Refractory-Non-Hodgkin-Lymphoma-and-Plan-to-Initiate-Pivotal.html

Slides https://ir.allogene.com/static-files/7a26a1c0-55f9-4474-a362-9a49b598c43c

[jondoeuk]

The poster https://www.allogene.com/resources/download/AACR-2021-PD1-iTurboCAR.pdf

[jondoeuk]

Link to the webcast https://allogene.zoom.us/webinar/register/WN_nyDYMLTnR9yi19rJRu-1kA

[jondoeuk]

Longer term data from the ALLO-501 PhI (ALPHA) trial will be presented alongside initial data from the PhI ALLO-501A (ALPHA2) trial at ASCO. There will be a separate presentation on ALLO-647, to include safety and PK/PD data

ALLO-501A, is intended for a potentially pivotal PhII trial, which should start in 2H, Previously it has been granted FDA fast track for R/R DLBCL. The company will host a webcast to review the data sets on May 19, at 2:30 pm PT/5:30 pm ET.

[jondoeuk]

An internal program (to overcome rejection) will downregulating MHC Class I expression and adding an NK cell inhibitory receptor antibody. Also, improvements are being made to the ex vivo expansion, with the use of defined populations of T-cells, of certain phenotypes (this achieved with cytokines and/or an anti-CD3/CD28 nanomatrix). In addition, RNAi to inhibit certain activity, such as EBAG9, which increases the release of cytolytic granules and/or granzyme- containing secretory lysosomes.

[jondoeuk]

From AACR:

CAR T cell therapy has attained unprecedented success in the treatment of hematological malignancies. However, clinical benefit in solid tumor indications has been limited, potentially in part due to suppressive solid tumor microenvironments (TME) that inhibit T cell effector function and persistence. While the provision of cytokine support can help CAR T cells overcome suppressive TME, combining CAR T therapy with systemically-administered cytokines/cytokine mimetics can result in toxicities and locally secreted cytokines may enhance rejection of allogeneic cell products by host cells. For this reason we had previously designed and tested a novel cytokine-stimulated CAR T cell designated TurboCARs. TurboCAR T cells coexpress a CAR and a Turbo domain (i.e. a homodimeric cytokine receptor chimera) that transmits CAR T cell-intrinsic cytokine signals, resulting in enhanced potency, expansion and persistence in preclinical studies. However, TurboCAR T cells may remain sensitive to inhibition by immune barriers, such as negative signaling through the PD1 receptor. We reasoned that a two-pronged approach aimed at inhibiting immune-suppressive PD1 signaling while simultaneously transmitting immune-potentiating cytokine signaling may augment CAR T cell activity in solid tumors. To this end, we engineered PD1 TurboCAR T cells, in which the Turbo domain is fused to a PD1 ectodomain that serves as a dominant-negative receptor. The PD1 ectodomain was further modified for high-affinity binding to PD1 ligands, allowing for preferential ligand sequestration and more effective inhibition of endogenous PD1 signaling. Despite having a larger lentiviral vector cargo, PD1 TurboCAR T cell products remained manufacturable and retained a favorable memory phenotype. PD1 TurboCAR T cells directed towards PDL1-expressing solid tumor target cells showed increased functionality compared to CAR T cells combined with PD1 blockade or to the parental TurboCAR T cells alone. In conclusion, PD1 TurboCARs augmented with a PD1 dominant negative ectodomain conferred CAR T cells with resistance to PD1-mediated inhibition, while simultaneously transmitting cytokine signals in a CAR T cell-intrinsic fashion. As an all-in-one product, PD1 TurboCAR T cells may obviate the need for combination therapy with anti-PD1 antibodies, while circumventing safety risks associated with systemic cytokine administration.

https://www.abstractsonline.com/pp8/#!/9325/presentation/2621

[jondoeuk]

From the recent call, ALLO have disclosed they are already designing next-gen TurboCARs to overcome immunosuppressive TMEs, particularly in solid tumours by engineering T-cell stimulatory domains that are activated by certain factors, such as PD-L1 and TGFb. Also, in concert with Baylor College of Medicine, are exploring the use of alloimmune defense receptors (to overcome rejection) [1].

Other planned improvements include manufacturing and CAR engineering. On top of this, there are twelve solid tumour targets, with two (CD70 [2,3] and DLL3 [4,5]) disclosed.

Refs:
1 https://www.nature.com/articles/s41587-020-0601-5
2 https://www.allogene.com/resources/download/AlloCAR-T-Targeting-CD70-For-RCC.pdf
3 https://www.mdpi.com/2072-6694/11/10/1611/htm
4 https://www.allogene.com/resources/download/Screening-and-Characterization-of-AlloCAR-T.pdf
5 https://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.TPS2597

[jondoeuk]

Preclinical data (ASH) https://ashpublications.org/blood/article/136/Supplement%201/8/472830/Preclinical-Evaluation-of-ALLO-605-an-Allogeneic