On November 15, 2021 Ayala Pharmaceuticals, Inc. (Nasdaq: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare and aggressive cancers, primarily in genetically defined patient populations, reported financial results for the period ended September 30, 2021 and highlighted recent progress and upcoming milestones for its pipeline programs (Press release, Ayala Pharmaceuticals, NOV 15, 2021, View Source [SID1234595544]).

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"As we gear up for multiple important milestones in 2022 across all of our clinical-stage programs in various indications, including desmoid tumors, triple negative breast cancer, adenoid cystic carcinoma and potentially multiple myeloma, we remain steadfast in our approach to developing gamma secretase inhibitors to treat these genetically defined cancers," said Roni Mamluk, Ph.D., Chief Executive Officer of Ayala. "We are incredibly pleased with the safety and efficacy profile of AL101 for the treatment of recurrent/metastatic adenoid cystic carcinoma harboring Notch-activating mutations, as presented at ESMO (Free ESMO Whitepaper) in September, as well as the strong preclinical rationale for potential combination treatment in this indication and other tumor types. We also continued to progress our pivotal RINGSIDE trial evaluating AL102 for the treatment of desmoid tumors as enrollment continues across multiple sites globally and look forward to reporting preliminary results from this trial in mid-2022. In addition, we are very pleased with our ongoing collaboration with Novartis and the status of the study of our AL102 in combination with their anti BCMA agent for multiple myeloma."

Recent Business Highlights and Upcoming Milestones:

Published Two Case Studies Highlighting Clinical Activity of AL101 in Desmoid Tumors in Current Oncology: In September 2021, Ayala published two case studies of adult patients with desmoid tumors treated with AL101. Both patients experienced significant tumor burden and symptomatic and life-threatening disease due to disease bulk and location. With AL101 treatment, both subjects achieved long-lasting partial responses with a maximal decrease in tumor size from baseline of 41% after approximately 1 year (55 weeks) of treatment in Case One, and a maximal decrease in tumor size from baseline of 60% after about 1.6 years (82 weeks) of treatment in Case Two.

On Track to Report Initial Interim Data from Part A of the Pivotal Phase 2/3 RINGSIDE Trial for the Treatment of Desmoid Tumors in Mid-2022: Enrollment continues to progress globally in the Phase 2/3 RINGSIDE Trial of AL102. Ayala expects to report an initial interim data read-out from part A of the trial in mid-2022, with part B of the study commencing thereafter.

Phase 1 Trial of AL102 in Combination with Novartis’ BCMA Targeting Agent, WVT087 for the Treatment of Relapsed/Refractory Multiple Myeloma Continues to Progress: Enrollment progresses as planned in the Phase 1 combination trial of AL102 with Novartis’ investigational anti-B-cell maturation antigen (BCMA) agent, WVT078, for the treatment of relapsed and/or refractory (R/R) multiple myeloma (MM).

Presented Preliminary Clinical Data from the Ongoing Phase 2 ACCURACY Trial and ACC at European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2021: In September 2021, Ayala presented updated interim data from the 6mg cohort of its ongoing Phase 2 ACCURACY study of AL101 for the treatment of recurrent/metastatic adenoid cystic carcinoma (R/M ACC) harboring Notch activating mutations. The data demonstrated meaningful clinical activity of AL101 6mg monotherapy with a 70% disease control rate across 33 evaluable patients. Partial responses were observed in three subjects (9%) and stable disease was observed in 20 subjects (61%). The 6mg dose of AL101 was well tolerated with manageable side effects consistent with those observed in the 4mg cohort.

Presented Preclinical Proof of Concept Data of AL101 in Combination with Approved Cancer Therapies in ACC at ESMO (Free ESMO Whitepaper): In September 2021, Ayala also presented a preclinical study evaluating the potential of combination therapy of AL101 in PDX models of ACC, comparing the differential gene expression of ACC tumors versus normal matched tissue regardless of Notch activation status. AL101 in combination demonstrated significant tumor growth inhibition, including regressions, compared to each drug alone, and the study indicated that crosstalk between signaling pathways may increase the efficacy of AL101 in R/M ACC regardless of Notch mutational status.

Phase 2 TENACITY Trial of AL101 for the Treatment of Triple Negative Breast Cancer Continues to Progress: Ayala continues to enroll patients in the Phase 2 TENACITY clinical trial of AL101, for the treatment of patients with Notch-activated recurrent or metastatic (R/M) triple negative breast cancer (TNBC). The Company expects to report preliminary data from this ongoing trial in 2022.

Third Quarter 2021 Financial Results

Cash Position: Cash and cash equivalents were $40.8 million as of September 30, 2021, as compared to $42.0 million as of December 31, 2020.
Collaboration Revenue: Collaboration revenue was $0.6 million for the third quarter of 2021, as compared to $0.7 million for the same period in 2020.
R&D Expenses: Research and development expenses were $7.4 million for the third quarter of 2021, compared to $5.4 million for the same period in 2020. The increase was primarily driven by the advancement in our clinical trials.
G&A Expenses: General and administrative expenses were $2.2 million for the third quarter of 2021, compared to $1.9 million for the same period in 2020.
Net Loss: Net loss was $9.8 million for the third quarter of 2021, resulting in a basic and diluted net loss per share of $0.68. Net loss was $7.4 million for the same period in 2020, resulting in a basic and diluted net loss per share of $0.59.

On November 15, 2021 Chimeric Therapeutics Presented the Corporate Presentation (Press release, Chimeric Therapeutics, NOV 15, 2021, View Source [SID1234595539])

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On November 15, 2021 ERYTECH Pharma (Nasdaq & Euronext: ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported the acceptance of an abstract with the results of its expanded access program (EAP) evaluating eryaspase in acute lymphoblastic leukemia (ALL) for poster presentation at the upcoming 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, which will be held from December 11-14, 2021, both in Atlanta, Georgia and virtually (Press release, ERYtech Pharma, NOV 15, 2021, View Source [SID1234595525]).

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Abstract #1214: Expanded Access Program: Evaluating Safety of Erythrocytes Encapsulating L-Asparaginase in Combination with Polychemotherapy in Patients Under 55 Years Old with Acute Lymphoblastic Leukaemia (ALL) at Risk to Receive Other Formulations of Asparaginase

The eryaspase Expanded Access Program (EAP) was conducted at ten clinical sites in France and enrolled 18 patients. The EAP evaluated tolerability and biological efficacy in patients under 55 years of age with ALL, unable or at risk to receive any other available asparaginase formulation. Patients in this study had developed hypersensitivities to prior E-Coli- and Erwinia-derived asparaginase therapies.

Hypersensitivity is the most common cause of truncated asparaginase therapy which has been associated with decreased event free survival. In the EAP and consistently across eryaspase ALL studies, including the NOPHO1 study, eryaspase provides a sustained asparaginase enzyme activity level with few hypersentivity reactions and is generally well tolerated in combination with chemotherapy.

Eryaspase provides a promising additional option for patients for whom further asparaginase treatment is contraindicated. The company intends to move forward towards the submission of a BLA to the US Food and Drug Administration (FDA) for eryaspase in hypersensitive patients.

The study findings will be presented as a poster presentation by Prof Dr. Yves Bertrand, Institute of Pediatric Hematology and Oncology, Civil Hospital of Lyon, Lyon, France.

On November 15, 2021 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Pantherna Therapeutics GmbH (CEO: Klaus Giese, Ph.D., "Pantherna") reported that the companies have entered into a technology evaluation agreement for the research of mRNA-based regenerative medicine (Press release, Astellas, NOV 15, 2021, View Source [SID1234595523]).

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Pantherna has a technology platform consisting of unique mRNA molecules (PTXmRNAs) for enhancing the efficiency of mRNA actions in the body, and lipid nanoparticles (PTXΔLNPs) for efficiently delivering mRNA.

Under this agreement, Pantherna’s state-of-the-art mRNA platform and Astellas’ high drug discovery capabilities will be utilized to promote research on the creation of new programs in the field of regenerative medicine and their application to treatment.

Astellas will be in charge of technology evaluation research aimed at providing drug discovery ideas and creating a therapeutic modality, and Pantherna will provide technical information and prepare candidate compounds for the technology evaluation research.

"We are excited and honored to collaborate with Astellas," said Pantherna’s Chief Executive Officer, Klaus Giese, Ph.D. "Astellas is an excellent partner for leveraging the unique aspects of our proprietary therapeutic mRNA technology, and this applied research is very important for the validation and broader application of the Pantherna mRNA technology in indications with high medical need."

"Astellas is engaged in the development of novel therapies using a new modality / technology based on the Focus Area approach strategy," said Taiji Sawamoto, Executive Vice President, Applied Research & Operations, at Astellas. "Pantherna is a leader in this area with a unique technology platform for mRNA. Through this collaboration, we will create an innovative regenerative medicine program with mRNA as a therapeutic modality, and we expect that we will be able to expand the treatment options of various diseases for which there has been no cure thus far."

On November 14, 2021 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, reported the presentation of three posters at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Washington D.C. (View Source) (Press release, Antengene, NOV 14, 2021, View Source [SID1234595529]).

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"Antengene is very pleased to present preclinical data on two of our Phase I programs, for ATG-101 and ATG-017, at the 2021 SITC (Free SITC Whitepaper) meeting on November 12, 2021. The unique mechanisms, promising preclinical safety and activity of these exciting new compounds are very much in keeping with Antengene’s mission to develop first-in-class, best-in-class medicines for cancer," said Jay Mei, M.D., Ph.D., Founder, Chairman and Chief Executive Officer of Antengene.

Dr. Mei continued, "These presentations also highlight the breadth and depth of Antengene’s drug development capabilities. The Antengene management team and I look forward to reviewing these posters, detailed below, and the Company’s exciting portfolio at our upcoming R&D Day, planned for November 16th (virtual, details below) and November 18th (in person, details below)."

Summary of Poster Presentations

Poster #893: ATG-101: Active in "Cold" tumors, No Preclinical Liver Toxicity

ATG-101 is a PD-L1 / 4-1BB bi-specific antibody that was designed to activate tumor infiltrating lymphocytes and inhibit immune checkpoints, without inducing liver toxicity. Antengene presented data from in vitro and in vivo studies that evaluated ATG-101 activity in several T-cell activation assays and multiple in vivo models, including those resistant to anti-PD(L)1 therapies.

Data in the poster showed that ATG-101 was active in anti-PD-L1 resistant and relapsed tumor models. In addition, ATG-101 increased the activation of T-cells and exhausted T-cells upon PD-L1 crosslinking (required for ATG-101 activity), rendering "cold" tumors "hot". Importantly, ATG-101 showed no liver toxicity in a GLP toxicity study (differentiating the drug vs other 4-1BB targeted monoclonals/bi-specifics) and did not induce cytokine release syndrome in an in vitro assay. ATG-101’s unique safety and efficacy properties make it a promising potential therapy for solid tumors and non-Hodgkins lymphoma.

Poster #608: Promising ATG-017 in vivo Combination Study Add to Clinical Strategy

ATG-017 is a potent small molecule kinase inhibitor targeting the extracellular signal-related kinases 1 and 2 (ERK1/2). Antengene presented data on an in vivo study that evaluated ATG-017 in combination with an anti-PD-L1 monoclonal antibody (atezolizumab), in an aggressive, immune checkpoint inhibitor resistant mouse cancer model.

Data in the poster showed that the combination enhanced the antitumor efficacy as well as increasing the percentage of infiltrating CD8+ T cells, NK cells, CD8:CD4 ratio and M1:M2 macrophage ratio in the tumor microenvironment, rendering a "cold" tumor "hot". These results demonstrated that ATG-017 has potential synergy with immune checkpoint inhibitors, providing a rationale for exploring combination therapy in the clinic in the pursuit of improved efficacy in solid tumors, including those resistant to checkpoint inhibitions.

Poster# 227: Computational Analysis Tool Enables ATG-101 Clinical Dose Selection

Bispecific antibody ATG-101 acts by forming a trimer (comprised of ATG-101 bound to PD-L1 and 4-1BB expressing cells) that activates tumor infiltrating lymphocytes and inhibits immune checkpoints. Measuring trimeric complexes is important in defining optimal clinical doses but is very challenging to do in the clinic.

Antengene and its collaborators at Applied BioMath, LLC reported on the development of a computational semi-mechanistic pharmacology model that could be used to define the clinical dose of ATG-101. It works by simulating in vivo tumor growth inhibition and predicting trimer formation, free drug levels and receptor occupancy over time. This work has enabled Antengene to define a clinically effective dose range of ATG-101 that induces >90% PD-L1 receptor occupancy, a key metric of drug activity. This valuable pharmacology tool, which may also be applied across other compounds in Antengene’s pipeline, reflects the Company’s enthusiasm to utilize novel technologies and partnerships to enhance drug development capabilities.

Details on the posters, published on the SITC (Free SITC Whitepaper) website, are shown below:

Abstract Number: 227
Title: A computational semi-mechanistic pharmacology model of ATG-101, a PD-L1/4-1BB bispecific antibody for treatment of solid tumors and NHL
Time: 7:00-17:00 EST, November 12-14, 2021
Presenter：Dr. David C. Flowers, Applied BioMath, LLC
First Author: Dr. David C. Flowers, Applied BioMath, LLC

Abstract Number: 608
Title: Synergistic effect of the combination of ATG-017, an ERK1/2 inhibitor, and immune checkpoint inhibitor in preclinical cancer models
Time: 7:00-17:00 EST, November 12-14, 2021
Presenter：Dr. Bing Hou, Antengene Corporation Limited
First Author: Dr. Peng Chen, Antengene Corporation Limited

Abstract Number: 893
Title: ATG-101, a novel PD-L1/4-1BB bispecific antibody, augments anti-tumor immunity through immune checkpoint inhibition and PDL1-directed 4-1BB activation
Time: 7:00-17:00 EST, November 12-14, 2021
Presenter：Dr. Bing Hou, Antengene Corporation Limited
First Author: Dr. Hui Yuwen, Antengene Corporation Limited

About ATG-101

ATG-101 is a novel PD-L1/4-1BB bi-specific antibody being developed for the treatment of multiple kinds of cancer. ATG-101 can activate anti-tumor immune effectors by simultaneously blocking the binding of PD-L1/PD-1 and inducing 4-1BB stimulation. In PD-L1 over-expressed cancer cells, ATG-101 has shown potent PD-L1 crosslinking-dependent 4-1BB agonist activity, thus potentially enhancing therapeutic efficacy, whilst mitigating risk of hepatoxicity. Antengene has received U.S. FDA approval for the IND for a Phase I trial of ATG-101 in solid tumors and non-Hodgkins lymphoma and is currently conducting a Phase I study of ATG-101 in Australia for the treatment of patients with metastatic/advanced solid tumors and non-Hodgkin lymphoma.

About ATG-017

ATG-017 is a potent and selective small molecule extracellular signal-regulated kinases 1 and 2 (ERK1/2) inhibitor. ERK1/2 are related protein-serine/threonine kinases that function as terminal kinases in the RAS-MAPK signal transduction cascade. This cascade regulates a large variety of cellular processes, including proliferation. The RAS-MAPK pathway is dysregulated in more than 30% of human cancers with the most frequent alterations being observed in RAS or BRAF genes across multiple tumor types. An ERK inhibitor enables the targeting of both RAS and BRAF mutant diseases. In nonclinical pharmacology studies, ATG-017 has demonstrated potent inhibition of ERK1/2 enzyme activity and tumor growth in vitro and in vivo. Antengene is conducting an open-label Phase I, dose-escalation study of ATG-017 in Australia for the treatment of patients with advanced solid tumors and hematologic malignancies.

About Antengene’s R&D Day

Antengene’s R&D Day will include presentations from Dr. Jay Mei, Founder, Chairman and CEO; Mr. John Chin, Chief Business Officer; Dr. Kevin Lynch, Chief Medical Officer; Dr. Bo Shan, Chief Scientific Officer, and other Company management.

The meetings will be held virtually in English on November 16, 2021, and on-site in Mandarin on November 18, 2021. A live webcast will be available on the Antengene website under "Investor Relations", on the Event Calendar page.

To attend the event, please register in advance at links below:

R&D Day English Session – Virtual Conference
Date: Tuesday, November 16, 2021
Time: 8:30 am – 11: 30 am, Eastern Time / 9:30 pm – 12: 30 am, Beijing Time
Register at: View Source
R&D Day Mandarin Session – Live Webcast of On-Site Meeting

Date: Thursday, November 18, 2021
Time: 1:30 pm – 5:30 pm, Beijing Time
Register at: View Source