On April 17, 2023 Myricx Pharma, an oncology drug discovery company focused on developing precision medicines based on its N-myristoyltransferase (NMT) platform has unveiled its antibody drug conjugate (ADC) programme, reported in vivo data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s Annual Meeting, AACR (Free AACR Whitepaper) 2023, April 14-19, Florida (Press release, MyricxBio, APR 17, 2023, View Source [SID1234635232]).

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!

NMT inhibitors (NMTi) have previously been shown to inhibit viability and growth of haematological cancers. Myricx’s novel highly potent NMTi are selectively cytotoxic in multiple cancer cell lines as well as exhibiting tumour regression in in vivo models of both haematological and solid cancers. Myricx has also developed a transcriptional signature which predicts cancer cell sensitivity to NMTi with high confidence.

Myricx’s advanced chemistry offers the potential for the development of NMTi as a novel payload on a wide range of existing linker and antibody ADC technologies. A unique feature of NMTi-ADCs is that they contain two targeting mechanisms: a monoclonal antibody (mAb) that targets the payload to antigen positive cancer cells; and selectivity for specific cancers with high intrinsic sensitivity to NMTi. Myricx has data elucidating the mechanism of this sensitivity.

Myricx’s most advanced ADC, MYX2449, is a selective and ultrapotent NMTi conjugated via a cleavable linker to trastuzumab (HER2+ mAb). Positive in vitro and in vivo data presented at AACR (Free AACR Whitepaper)2 demonstrate MYX2449 cytotoxic potency in selective cancer cell lines, anti-tumour efficacy in both high and low HER2 expressing cancers, with tolerability >10 times its efficacious dose in in vivo models.

As a proof of concept (PoC) for its NMTi-ADC approach, Myricx tested MYX2449 trastuzumab-NMTi ADC in in vivo models of gastric cancer (GC) and breast cancer (BC), as many of these cancers express HER2 and also express the NMTi sensitivity signature. MYX2449 delivered differentiated activity and improved efficacy compared to the gold standard ADC trastuzumab-deruxtecan in a GC model with excellent tumour shrinkage at 5mpk in the xenograft and excellent cyno tolerability at the highest dose, 20mpk. Similar efficacy was obtained in a BC xenograft model.

Encouraged by these positive PoC results, Myricx is now exploring a range of ADCs in further hard-to-treat solid cancers that express both the NMTi sensitivity signature and ADC-compatible antigens.

Myricx CEO Dr Robin Carr who presented the ADC-NMTi poster at AACR (Free AACR Whitepaper) said "NMT inhibitors represent a novel class of ADC payloads that can be exploited as targeted therapies in cancer. Based on our positive PoC data we believe that ADC-NMTi offer huge potential for selective cancer cell killing via its unique mechanism of action."

Myricx is a start-up from two of London’s leading biomedical research organizations, Imperial College London and the Francis Crick Institute. Myricx scientists and founding collaborators were the first to identify that inhibition of NMT is highly effective in the treatment of MYC-driven cancer models acting through the unfolded protein response (UPR). UPR stress is a known vulnerability of cancer and Myricx is now using its discoveries to build a proprietary pipeline of targeted cancer therapies. The company is developing NMTi as small molecule drugs as well as novel selective cytotoxic payloads for ADCs.

In addition to the poster on its lead ADC programme, scientists from Myricx’s collaborators presented two posters on Myricx’s small molecule programmes and NMT biology, including in vivo reprogramming of tumour-associated macrophages to an anticancer phenotype by modulating NMT activity1 and how deregulation of MYC-family proteins sensitizes cancers to NMT inhibition, resulting in the identification of NMTi sensitivity and mechanism.3

Professor Ed Tate, Myricx co-founder and lead author of the posters presented by the Imperial College London/Francis Crick Institute teams said "NMT is a hot emerging drug target in cancer and Myricx has developed high-quality proprietary chemical inhibitors of NMT that have led to breakthrough discoveries and unlocked an unexpected and unique mechanism of cancer cell killing, specific to cancers with vulnerabilities associated with the unfolded protein response. Furthermore, we have recently shown that NMTi has the potential to drive anti-tumour innate immune responses, including the reprogramming of tumour-associated macrophages in the tumour microenvironment.

"These discoveries alongside the massive potential of NMTi as a selective ADC payload pave the way for novel and highly efficacious treatments for patients."

1. Poster number: 439: From foe to friend: In vivo reprogramming of tumour-associated macrophages to an anti-cancer phenotype by modulating N-myristoyltransferase activity – presented by @Wouter Kallemeijn, Francis Crick Institute/Imperial College London
New Drug Targets 16 April 1:30 PM Section 16 board 3

2. Poster number: 2635: N-Myristoyltransferase (NMT) inhibitors as novel potent payloads for antibody drug conjugates – presented by our CEO @Robin Carr
Antibody Technologies session 17 April, 1:30 PM Section 13 board 3

3. Poster number: 4871: Dysregulation of MYC-family proteins sensitizes cancers to NMT inhibition: identification of NMTi sensitivity and mechanism – presented by @James Zhang, ICR/Imperial College London
Anticancer Approaches Targeting Signal Transduction Pathways 18 April 1:30 PM Section 13 board 14

Copies of these posters will be available on our website after they have been presented – view posters

On April 17, 2023 Etira reported multiple abstracts related to their licensed products showed encouraging preclinical activity in metastatic breast cancer and ovarian cancer (Press release, EtiraRx, APR 17, 2023, View Source [SID1234632165]). The data, presented at The American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, demonstrate strong efficacy in multiple preclinical models both in vitro and in vivo.

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 by the positive preclinical results for both ERX-208 and ERX-41 recently presented at AACR (Free AACR Whitepaper). Our studies validate our prior finding that targeting LIPA to induce endoplasmic reticulum stress can effectively overcome tumor heterogeneity in ovarian cancer cells," said Russell Hayward, Chief Executive Officer of Etira. "We are especially encouraged by preclinical data that demonstrates ERX-208 is a highly potent agent against ovarian cancer and can be advanced to clinical trials. We are also excited by the preclinical data supporting the use of a chemically distinct analog TX-245 in metastatic breast cancers driven by the mutant estrogen receptor. These findings support our pipeline of agents for additional indications, as we continue to advance ERX-315 to clinical trials."

Presentations included:
1. ERX-208 as a novel therapeutic for treating ovarian cancer by enhancing endoplasmic reticulum stress (poster)
Presenter: Suryavathi Viswanadhapalli
Conclusions: The data demonstrated the utility of ERX-208 in ovarian cancer to overcome tumor heterogeneity by targeting LIPA and enhancing endoplasmic reticulum stress leading to apoptosis. ERX-208 reduced the growth of OCa patient derived organoids in vitro, patient derived explants ex vivo and xenografts including patient derived xenografts in vivo. ERX-208 treatment did not show any signs of toxicity at doses administered.

2. Novel LIPA targeted therapy for treating ovarian cancer (poster)
Presenter:Alexia B. Collier
Conclusions: These studies indicate that ERX-41 effectively binds to and targets LIPA, induces endoplasmic reticulum stress and apoptosis of multiple types of ovarian cancer cells. Detailed molecular characterization of how ERX-41 binding to LIPA induces ER stress in OCa cells is ongoing.

3. Targeting the mutant estrogen receptor in metastatic breast cancer (talk)
Presenter:Karla Parra
Conclusions:TX-245, which was designed to bind to the mutant estrogen receptor, effectively inhibits cell proliferation in cell lines that express WT or mutant ESR1, induce ER degradation, suppress ER-mediated signaling and reduce tumor burden in mouse models. Importantly, TX-245 inhibited the progression of metastatic tumors, indicating its potential utility in patients with metastatic breast cancer expressing the mutant estrogen receptor.

On April 17, 2023 Champions Oncology, Inc. (NASDAQ:CSBR), a leading global technology-enabled research organization that is transforming drug discovery through innovative AI-driven pharmaco-pheno-multiomic (PPMO) integration, reported the launch of its therapeutic discovery and development platform into a wholly owned subsidiary named Corellia AI (Corellia) (Press release, Champions Oncology, APR 17, 2023, View Source [SID1234630517]). Corellia launches out of Champions Oncology with a team of world class scientists advancing a robust pipeline of therapeutic programs and a unique discovery and development platform. The company will continue to leverage Champions’ superior PDX Molecular Atlas and its living bank of PDX models as central tools in its proprietary target and therapeutic discovery platform.

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 comprehensive discovery platform established by Corellia boasts AI-mediated technology that yields an extremely deep and continuously growing pool of novel therapeutic targets, and AI-guided technology for the discovery of novel therapeutic chemistry. Corellia’s objective is to develop innovative first-in-class Antibody Drug Conjugates (ADCs) for patients with high unmet needs, at a pace and efficiency never achieved before.

Ronnie Morris, MD, President and CEO of Champions Oncology, who will also serve as Executive Chairman of Corellia AI said "I’m thrilled about the formation of Corellia. The therapeutic discovery initiative at Champions has been an exciting endeavor that utilizes our deep data. This team has been very effective at identifying interesting novel targets and has rapidly built therapeutic programs around these targets. So, launching this into a wholly-owned subsidiary has been a natural next step, and will allow us to facilitate future growth. I look forward to seeing the continued growth and success of this organization as we enter this next phase."

"The evolution of Champions’ therapeutic discovery and development initiative into an early-stage biotech has been a thrilling experience," said Michael Ritchie, PhD, M.B.A, Chief Commercial Officer at Champions Oncology who will serve as Chief Executive Officer of Corellia AI. "The discovery platform built by the Corellia team is truly unique, and it has enabled the development of an exciting set of early therapeutic programs. We have plans to aggressively move these programs into the clinic and leverage our unparalleled platform to continue building a very deep pipeline of additional therapeutic programs. Our current focus is on the development of transformative and novel next-generation Antibody Drug Conjugates, and the Corellia platform is capable of much more in the future."

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.