Genocea Biosciences Inc (EM) (GNCAQ)

Effective Dec. 23,2022 GNCA will change to GNCAQ, bankruptcy.

https://otce.finra.org/otce/dailyList?viewType=Symbol%2FName%20Changes

Comeback time

DTIL covers with better money and partners similar territory/platforms, so just holding for positives before the necessary negatives.

The collab is focused on advancing multiple existing and additional next gen allo CAR-T programs directed to haematological malignancies. RHHBY has an exclusive license to anti-BCMA and anti-CD19/CD20 programs. Exclusive option to anti-CD70 and anti-BCMA/CD19 programs, as well as the right to nominate six additional candidates.

PSTX

$62M in valuation, assets and cash, and selling for $1.2M market capitalization. There is a merger coming here for sure, they are preparing this for a reverse merger, as the recent filings suggest. Somebody is buying all those shares up!

GNCA featured in Microcapdaily : https://microcapdaily.com/genocea-biosciences-inc-otcmkts-gnca-ex-nasdaq-biotech-heating-up-and-making-moves-on-the-otc-as-co-winds-down-operations/

It means whatever was in the S-8 has now become effective.

What does notice of effectiveness mean?

This is starting to tick back up now.....

GNCA delisted from the Nasdaq to the OTC:

https://otce.finra.org/otce/dailyList?viewType=Additions

Not sure about Fraud. They just went out of business. Shut down operations and laid off everyone. Just didn't work out.

Plain and simple - FRAUD!!!!!

The CEO and BOD should be thrown in jail for stealing salaries for nothing.

Fraud!!

Leerink Partners should feel pretty stupid right about now.

https://www.tipranks.com/news/blurbs/genocea-biosciences-gnca-receives-a-buy-from-leerink-partners?utm_source=advfn.com&utm_medium=referral

Ouch

Preclinical posters

Engineering TGF-B-resistant TCR-edited T cells for mutant TP53-targeted cancer immunotherapy https://www.neogene.com/staging/wp-content/uploads/2022/04/Keystone-2022-TGFBR2-KO-TP53-R175H-TCR-poster-final-edit.pdf

Development of a personalized neoantigen specific TCR discovery platform https://www.neogene.com/staging/wp-content/uploads/2022/04/Neogene-Poster-v1-final_reduced.pdf

ATLAS worked. Planet failed.

T cells that show up in great numbers in head and neck tumors, but not in similar tissues of the mouth inflamed by common ailments such as gum disease.

It seems that this odd group of T cells have mixed up their highly specialized assignments within our immune systems and are now working to protect tumor cells.

PR https://www.prnewswire.com/news-releases/pact-pharma-highlights-capabilities-and-versatility-of-novel-non-viral-gene-editing-technology-in-presentation-at-american-society-of-gene--cell-therapy-asgct-25th-annual-meeting-301547277.html

Poster https://storage.googleapis.com/pact-assets/ASGCT-2022-Lu/ASGCT-2022-Lu.pdf

''NT-125 is an investigational, autologous, fully-individualized, multi-specific TCR therapy targeting neoantigens for the treatment of advanced solid tumors. NT-125 is designed to contain up to five distinct neoantigen-specific TCRs per patient in a single cell product of highly functional engineered T cells, allowing multiple neoantigens presented by HLA class I and HLA class II molecules to be targeted with the goal to create a more impactful TCR therapy for more patients. NT-125 aims to reduce the probability of antigen escape and potentially maximize the depth and durability of clinical responses in a patient population with difficult to treat tumors and high unmet need.'' https://www.biospace.com/article/releases/neogene-therapeutics-announces-approval-of-clinical-trial-application-for-its-first-phase-1-trial-of-novel-fully-individualized-tcr-therapy-to-treat-advanced-solid-tumors/

Also, https://www.businesswire.com/news/home/20220111005172/en/Neogene-Therapeutics-Announces-Exclusive-License-with-the-National-Cancer-Institute-for-a-Portfolio-of-T-Cell-Receptors-TCR-Targeting-KRAS-and-TP53-Mutations-for-the-Treatment-of-Cancer

189: A Versatile, Non-Viral Gene Editing Method for Directing Specificity and Enhancing Function of T Cells https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=1157

Hopefully, this will play out similar to MRK buying Immune Design (from memory, they had to cut the workforce by ~20% after the lead program was discontinued).

Biotechs are filled with frauds. Investors kept in the dark until the well runs dry.

CEO knew Planet failed when DP was made for cohort A.

NPT turned out to be a lost TIL. 10000 pg promised, 1000 pg IFN actual

Turnstone Bio https://www.businesswire.com/news/home/20220425005377/en/Turnstone-Biologics-Announces-TIL-Therapy-Research-Collaboration-with-the-University-of-Montreal-Hospital-Research-Centre

By Q4 (GEN-011)

20-24 patients dosed.

Day 57 scans from 14-18 patients.

Up to 10 patients on schedule B3 (TIL-like).

Day 113 scans from 9-11 patients.

Up to 8 patients on schedule B3 (TIL-like).

Tumour mix: NSCLC, SCCHN, UC, and melanoma likely to predominate.

Biomarker data: ctDNA, tumour infiltration, TCR sequencing and proliferation and persistence.

From this: ''Using high-dimensional analysis of human ACT products, we identified a memory-progenitor CD39-negative stem-like phenotype (CD39-CD69-) associated with complete cancer regression and TIL persistence and a terminally differentiated CD39-positive state (CD39+CD69+) associated with poor TIL persistence.'' https://www.science.org/doi/10.1126/science.abb9847

Also, ''With a median potential follow-up of 89 months, 46 of 48 complete responders in the aPD-1-naïve cohort have ongoing responses after a single treatment and 10-year melanoma-specific survival of 96%.'' https://aacrjournals.org/clincancerres/article-abstract/27/19/5289/671696/Impact-of-Prior-Treatment-on-the-Efficacy-of

Hopefully, a trial testing these double negative TIL in melanoma, as well as other types will be underway soon.

young” tumor infiltrating lymphocytes can mediate regression of metastatic melanoma
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978753/#SD1

Perspectives of tumor-infiltrating lymphocyte treatment in solid tumors
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-02006-4

Intratumoral CD40 agonist sotigalimab with pembrolizumab induces broad innate and adaptive immune activation in local and distant tumors
There was a robust upregulation of T cells, macrophages, CD8+ T cells, and cytotoxic gene signatures in responders. Additionally, responders had an increase in Th1 gene signatures; an increase in TGF-ß1 gene expression was also noted. In distant lesions, the same gene signatures were upregulated.

https://acir.org/weekly-digests/2022/april/aacr-annual-meeting-2022#therapies

Mellman described published work linking PD-1 and CD28 signaling through the phosphatase Shp2. Evidence also showed that myeloid cells, particularly dendritic cells in the TME, were the critical source of PD-L1 ligand.

https://acir.org/weekly-digests/2022/april/aacr-annual-meeting-2022#therapies

Bio chop suey : Orca-T is an investigational high-precision allogeneic cellular therapy consisting of infusions containing regulatory T-cells, conventional T-cells and CD34+ stem cells derived from peripheral blood from either related or unrelated matched donors.

The poster

Speaking of GvHD, Orca Bio (an IPO could be in the works) https://www.businesswire.com/news/home/20211211005011/en/Positive-Clinical-Results-from-More-than-100-Patients-Treated-with-Orca-Bio’s-Lead-Investigational-High-Precision-Cell-Therapy-Presented-at-63rd-ASH-Annual-Meeting

A PhIII (in AML, ALL and MDS) should be underway soon.

Some slides from a presentation given at ESMO '21 on the MAYA trial (eoesophageal types are MGMT low. Another group is investigating the approach in the ELEVATE trial).

High-Dose Cyclophosphamide Reduces Graft-Versus-Host Disease Following Stem Cell Transplantation

https://www.practiceupdate.com/content/ash-2019-high-dose-cyclophosphamide-reduces-graft-versus-host-disease-following-stem-cell-transplantation/94022

Emergence of tumor mismatch repair deficiency and increased mutational burden in blood and tissue of metastatic colorectal cancer patients treated with temozolomide

https://www.abstractsonline.com/pp8/#!/10517/presentation/20869

https://ascopubs.org/doi/full/10.1200/JCO.21.02583

The reason high-dose cyclophosphamide is able to ablate the effector cells without destroying hematopoietic stem cells is that the earliest stem cells (but not lymphocytes) contain high levels of aldehyde dehydrogenase conferring resistance to the cytoxic properties of cyclophosphamide. Dr. Brodsky and his colleagues in neurology and rheumatology are applying this approach in other severe autoimmune disorders including, scleroderma, myasthenia gravis, multiple sclerosis and autoimmune hematologic disorders.

https://ashpublications.org/blood/article/115/11/2136/27022/High-dose-cyclophosphamide-for-severe-aplastic

NeoPhore is developing first-in-class small molecule inhibitors to specifically block the MMR pathway in solid tumours. The company's scientific co-founders and SAB members Drs. Alberto Bardelli and Luis Diaz on new research showing that pharmacological inhibition of DNA mismatch repair can conceptually enhance patient responses to immunotherapy https://www.science.org/content/article/surprising-strategy-would-fight-mutant-cancer-cells-making-more-mutations

Fludarabine exposure predicts outcome after CD19 CAR T-cell therapy in children and young adults with acute leukemia

https://ashpublications.org/bloodadvances/article/6/7/1969/483864/Fludarabine-exposure-predicts-outcome-after-CD19

MC = 64 doses CAR T

T cells CPD

https://bmcimmunol.biomedcentral.com/articles/10.1186/s12865-021-00435-7

GNCA Buyers and sellers feel like TILS

Last Smart Money left the bldg. only dummies stick around.

Analysis of severe lymphodepletion on the day of TIL infusion as measured by absolute lymphocyte counts showed similar values when comparing the high-dose and low-dose cyclophosphamide/fludarabine groups (0.029 ± 0.036 K/L [median, 0.020 K/L] vs 0.024 ± 0.017 K/L [median, 0.025 K/L]).

https://www.healio.com/news/hematology-oncology/20210820/highdose-lymphodepletion-regimen-effective-but-more-toxic-for-patients-receiving-tils?msclkid=2e42737cc10911ecbba737c4032a5800

Cyclophosphamide alters the tumor cell secretome to potentiate the anti-myeloma activity of daratumumab

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849715/

Cyclophosphamide Enhances Cancer Antibody Immunotherapy in the Resistant Bone Marrow Niche

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780711/

The effect of low-dose IL-2 and Treg adoptive cell therapy in patients with type 1 diabetes

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492314/#sd

A PhI trial (NCT04217473) is assessing an 'armed' (encodes for hTNF-a and hIL-2) OV in R/R stage III/IV melanoma patients, who cannot be treated with curative intent and are eligible for TIL therapy. Patients receive TILT-123 intravenously and intratumorally, and TIL therapy without LD chemo or high-dose IL-2 https://www.businesswire.com/news/home/20220330005560/en/TILT-Biotherapeutics-Announces-Positive-Update-on-its-Phase-1-Immunotherapy-Clinical-Trials-in-Cancer