On April 17, 2023 ERYTECH Pharma (Nasdaq & Euronext: a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported that it received approval from The Nasdaq Stock Market LLC ("Nasdaq") dated April 12, 2023, to transfer the listing of its American Depositary Shares representing ordinary shares of the Company ("ADSs") from The Nasdaq Global Select Market to The Nasdaq Capital Market (Press release, ERYtech Pharma, APR 17, 2023, View Source [SID1234630234]). The transfer became effective at the opening of business on April 14, 2023.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Company’s ADSs continue to trade under the symbol "ERYP" and trading of its ADSs will be unaffected by this transfer. The Nasdaq Capital Market is a continuous trading market that operates in substantially the same manner as The Nasdaq Global Select Market.

The approval was based upon the Company meeting the applicable market value of publicly held shares requirement for continued listing and all other applicable requirements for initial listing on the Capital Market, except for the bid price requirement, the Company’s written notice of its intention to cure the deficiency by effecting a reverse stock split, if necessary, its agreement to the conditions outlined in the Nasdaq Listing Agreement, and additional supporting information provided in its application.

In connection with the transfer to the Nasdaq Capital Market, Nasdaq granted the Company an additional 180-day period (or until October 2, 2023) to regain compliance with the requirement set forth in Nasdaq Listing Rule 5450(a)(1) that the bid price of the Company’s ADSs meet or exceed $1.00 per ADS for at least ten consecutive business days. If at any time during this additional time period the closing bid price of the Company’s security is at least $1 per share for a minimum of 10 consecutive business days, Nasdaq will provide written confirmation of compliance and this matter will be closed.

On April 17, 2023 Parthenon Therapeutics, a precision oncology company discovering and developing a novel class of therapies that reprogram the tumor microenvironment (TME), reported data at the AACR (Free AACR Whitepaper) Annual Meeting 2023, on the high prevalence of immune exclusion in select solid tumor types (Press release, Parthenon Therapeutics, APR 17, 2023, View Source [SID1234630219]). The data further support Parthenon’s planned Phase 1 clinical trial of lead candidate PRTH-101, a novel Discoidin Domain Receptor (DDR1) inhibitor which targets DDR1-directed collagen barriers in immune excluded tumors. (NCT05753722)

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Patients with immune-infiltrated tumors have high levels of tumor-killing immune cells in contact with tumor cells and often respond to existing immunotherapies. However, most patients with solid tumors lack immune cells in physical proximity to tumor cells. This can be due to collagen barriers that prevent immune cells from reaching tumor cells in immune excluded tumors. DDR1 contributes to collagen barriers in the TME by aligning collagen fibers that prevent the infiltration of immune cells.

"These data revealing the high incidence of immune exclusion in a number of cancer types demonstrate the large unmet need that exists in the field of immuno-oncology, which often does not address barriers in the TME that prevent immune cell interaction and killing of tumor cells," said Laura Dillon, PhD, Vice President of Translational Medicine & Bioinformatics at Parthenon Therapeutics.

The findings released today show that greater than 40% of patient tumors in triple negative breast cancer, non-small cell lung cancer, pancreatic ductal adenocarcinoma, and colorectal cancer are immune excluded based on both pathologist-defined immune phenotypes and image analysis. Moderate levels of immune exclusion were observed in ovarian cancer, and low levels in sarcoma subtypes. Furthermore, Parthenon proposed methodologies to systemically characterize immune phenotypes– based on the analyses of immunohistochemistry images, demonstrating both the benefits and limitations of this approach as benchmarked against more traditional methods for defining immune phenotypes that rely on pathologist impression.

"There is a unique opportunity for PRTH-101 to address the largely neglected TME in patients with solid tumors. We look forward to providing updates in the coming months as we prepare to transition to a clinical stage company with the progression of our lead asset PRTH-101 into Phase 1 trials," commented G. Travis Clifton, MD, co-founder, Head of Clinical Science at Parthenon Therapeutics.

These data were generated in collaboration with Institute Bergonié (PI: Antoine Italiano). The poster detailing these findings – #2108 – will be presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on Monday, April 17, 2023.

About PRTH-101

PRTH-101 is a therapeutic antibody that specifically binds to and blocks DDR1, a protein expressed on tumor cells that binds collagen to make a minimally permeable physical barrier that blocks immune cells from interacting with and attacking tumor cells. Thus, these "immune cell-excluded" solid tumors are resistant to attack by the immune system (as well as other existing therapies). By disabling DDR1, the collagen fibers lose alignment and loosen, creating gaps in the tumor barrier, thus allowing T-cells to enter and naturally attack the tumor. The creation of DDR1-directed collagen alignment does not appear to have a normal physiological surrogate and may therefore be unique to pathologies such as neoplasia, potentially allowing for relatively safe interventions. Thus, blockade of DDR1 represents a unique and "orthogonal" approach to stimulating the immune-based antitumor activity, and such blockade shows both single agent anti-tumor activity as well as marked augmentation of immunity enhanced by PD-1 blockade.

Tumor types which show particularly high levels of DDR1-associated collagen barriers include colorectal, ovarian, and non-small cell lung cancer. Currently, there are no approved drugs that target DDR1.

On April 17, 2023 Boundless Bio, a clinical stage next-generation precision oncology company developing innovative therapeutics directed against extrachromosomal DNA (ecDNA) in oncogene amplified cancers, reported it will present at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, held in Orlando and virtually from April 14-19, 2023 (Press release, Boundless Bio, APR 17, 2023, View Source [SID1234630218]). The poster "Tumors driven by oncogene amplified extrachromosomal DNA (ecDNA) demonstrate enhanced sensitivity to cell cycle checkpoint kinase 1 (CHK1) inhibition" is available for in-person presentation on April 17, 2023 at 9:00 a.m. – 12:30 p.m. ET.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited to unveil CHK1 as the ecDNA-essential target for our first novel ecDNA-directed therapy (ecDTx)," said Christian Hassig, Ph.D., Chief Scientific Officer of Boundless Bio. "Leveraging our proprietary ecDNA-centric research platform, Spyglass, we identified CHK1 as an essential regulator of replication stress associated with oncogene amplification on ecDNA, revealing a unique, druggable, and cancer-specific liability. Our research revealed that ecDNA-enabled cancers have an exquisite reliance on CHK1 to manage intrinsically elevated replication stress, and this important discovery has led to the development of the first ecDTx, BBI-355. BBI-355, a potentially best-in-class, oral, and selective CHK1 inhibitor, is the subject of a recently initiated first-in-human Phase 1/2 clinical study."

Patients with tumors that harbor oncogene amplification on ecDNA have poor prognosis and generally do not respond well to targeted therapies and possibly immunotherapies. Boundless Bio has previously presented the relationship between oncogene amplification on ecDNA and DNA replication stress, a known form of genomic instability that contributes to oncogenesis and tumor evolution. Today we present data showing that cancer cells with oncogenes amplified on ecDNA are hyper-reliant on CHK1 to survive and that inhibition of CHK1 in ecDNA-enabled cancer cells is synthetically lethal. Using our Spyglass platform, we identified CHK1 as an ecDNA essential drug target through a CRISPR genetic screen and further pharmacologically validated its essential role in multiple ecDNA model systems across various tumor types and oncogene drivers.

We designed BBI-355, an orally available, highly potent, and selective inhibitor of CHK1 to target this unique genetic susceptibility in ecDNA-bearing cancer cells. In January of this year, the FDA accepted our investigational new drug application to enable the BBI-355-101 Phase 1/2 clinical trial of BBI-355, which is now open for enrollment of patients with oncogene amplified solid tumors.

About Extrachromosomal DNA (ecDNA)

ecDNA are circular units of nuclear DNA that are physically distinct from chromosomes and are found only within cancer cells. ecDNA encode full length genes, including oncogenes and regulatory regions, are highly transcriptionally active, and lack centromeres. ecDNA replicate and express within cancer cells and, due to their lack of centromeres, can be asymmetrically passed to daughter cells during cell division, leading to focal gene amplification and gene copy number heterogeneity in cancer. By leveraging the plasticity afforded by ecDNA, cancer cells can increase or decrease copy number of select genes located on ecDNA to enable survival under selective pressures, including targeted therapy, chemotherapy, or radiation, thereby making ecDNA one of cancer’s primary mechanisms of growth and treatment resistance. ecDNA are not found in healthy cells but are present in many cancers. They are a key driver of the most aggressive and difficult-to-treat cancers, specifically those characterized by high copy number amplification of oncogenes.

About BBI-355

BBI-355 is a potentially best-in-class checkpoint kinase 1 (CHK1) inhibitor and the first ecDNA-directed therapy (ecDTx) being investigated to treat patients with oncogene amplified cancers. CHK1 is a master regulator of DNA replication stress (RS), which frequently arises from oncogene amplification on extrachromosomal DNA (ecDNA). Inhibition of CHK1 by BBI-355 is synthetic lethal in cancer cells with oncogene amplification on ecDNA due to their heightened RS. CHK1 was identified and validated as an ecDNA essential target via Boundless Bio’s proprietary Spyglass platform and led to the development of BBI-355, an orally available, potent, and selective inhibitor of CHK1. BBI-355 is currently being evaluated in a first-in-human trial designed to evaluate the safety, maximum tolerated dose, and recommended Phase 2 dose of BBI-355 as a single agent and in combination with select therapies in patients with locally advanced or metastatic solid tumors with oncogene amplifications.

On April 17, 2023 Strand Therapeutics, the programmable mRNA company developing curative therapies for cancer and other diseases, reported preclinical data from its programmable mRNA therapy STX-001, a multi-modal synthetic self-replicating mRNA technology that delivers a prolonged and locally-acting IL-12 cytokine to the tumor microenvironment (Press release, Strand Therapeutics, APR 17, 2023, View Source [SID1234630217]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Immunotherapy has revolutionized cancer treatment, but only a minority of patients experience durable clinical responses. One of the reasons for this limited efficacy is the failure of immune checkpoint inhibitors to sufficiently activate and recruit T cells into the tumor microenvironment.

STX-001, when delivered directly to the tumor, induces a highly immunogenic tumor cell death while the mRNA-encoded IL-12 payload promotes recruitment of effector T cells and NK cells into the tumor microenvironment. STX-001 shows promise as a new approach to improve the efficacy of current immunotherapies for solid tumors. STX-001’s self-replicating mRNA technology induces immunogenic tumor cell death and promotes recruitment of T cells and NK cells to the tumor microenvironment as well as their activation.

"Our programmable mRNA therapy STX-001 overcomes the limitations of current immunotherapy to improve clinical responses to solid tumors. The major breakthrough is that we’ve shown for the first time our therapy enables the delivery of therapeutic quantities of IL-12 with greater efficacy than conventional mRNA," said Tasuku Kitada, Ph.D., President and Head of R&D of Strand Therapeutics.

"This early data also shows that STX-001 induces durable anti-tumor responses and enhances efficacy when combined with PD-1/PD-L1 checkpoint inhibitors. STX-001 represents a promising new approach for the treatment of solid tumors, and we look forward to advancing this candidate into clinical trials later this year," said Prashant Nambiar, DVM, Ph.D., Senior Vice President, Research and Translational Development.

On April 17, 2023 PIC Therapeutics, Inc., a biotechnology company pioneering the discovery and development of first-in-mechanism, first-in-class allosteric small molecule therapies targeting eIF4E, reported pre-clinical data today on the company’s advancing eIF4E program for breast cancer in a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, taking place in Orlando, FL (Press release, PIC Therapeutics, APR 17, 2023, View Source [SID1234630216]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Advanced or metastatic breast cancers represent a large patient population with limited long-term solutions that address both the heterogenous nature of resistant tumors and the aggressiveness of their proliferation. The aim of our therapies is to drive strong mechanistic responses, in a majority of breast cancer tumor subtypes, that induce a rapid commitment to cell death. To accomplish this, our approach addresses a key fundamental mechanism in protein translation at the convergence of many oncogenic signaling pathways through which resistance arises.

eIF4E is a key component of protein translation that often becomes dysregulated in breast cancer, supporting cell survival and metastasis alongside therapeutic resistance. PIC compound regulation of eIF4E induces rapid commitment to apoptosis and selective proteomic shifts that are consistent with canonical eIF4E regulation including cell cycle impacts, e.g. effects on cyclin family members and CDKs, DNA repair regulation and metabolic proteins. PIC Compounds also potently impact multiple clinical drivers for ER+ and Triple Negative Breast Cancers, which are evidenced by mRNA signatures that include changes consistent with proteomic impacts to key transcription factors.

Previous communications revealed our eIF4E regulators potently cause cell death in primary breast cancer organoid models, but spared models derived from healthy tissue. Expanding our efforts in this domain, the impact on normal immune cells was evaluated by exposing PBMCs, CD4+ T cells, and bone marrow mononuclear cells to our compounds. Our eIF4E regulators did not impair survival of these cells up to a maximum tested dose of 25 micromolar. Primary CD4+ T cells were also found to be functional in the presence of eIF4E regulators up to 5 micromolar, which included assessments of CD3/CD28 stimulated cytokine production and proliferative responses, highlighting its remarkable differentiated impact on normal cells compared to tumor cells.

"We continue to uncover interesting and distinctive preclinical data sets that underscore the potential for unique therapeutic advantages of allosterically regulating eIF4E, as a promising strategy for patients with various subtypes of breast cancer," said Kathy Bowdish, Ph.D., President and Chief Executive Officer of PIC Therapeutics.

Our findings suggest that allosteric regulation of eIF4E provides a unique and efficient way to address multiple resistance mechanisms while sparing normal immune cellular function. Our eIF4E regulators represent a potential beneficial therapeutic approach to address multiple resistant cancer patient populations and fulfill the promise of this elusive target.

Presentation details:

Title: eIF4E allosteric regulators cause rapid commitment to apoptosis in cancer cells while sparing immune cells

Session Category: Experimental and Molecular Therapeutics

Session Title: Novel Antitumor Agents 3

Session Date and Time: Monday April 17, 9:00 AM – 12:30 PM

Location: Section 17

Poster Board Number: 14

Abstract Number: 1624