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Carina Biotech and AdAlta to develop unique next-generation CAR-T cancer therapeutics

On August 27, 2021 Carina Biotech reported that has entered a collaboration agreement with Melbourne biotech AdAlta to develop precision engineered, i-body enabled CAR-T therapies that provide new hope for patients with cancer (Press release, Carina Biotech, AUG 27, 2021, View Source [SID1234586959]).

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This is a collaboration at the cutting-edge of cancer medicine, bringing together Carina’s world-leading proprietary CAR-T technologies with AdAdlta’s unique i-body platform. The agreement will develop i-body enabled CAR-T cancer immunotherapies against up to five solid tumour antigen targets.

The small size and unique targeting of i-bodies provides for greater flexibility and design options for CAR-T cells, which are ideally suited for the production of bi-specific CAR-T cells.

Bi-specific CAR-T cells have the potential to deliver precisions to difficult-to-target cancers – by targeting two antigens on cancer cells, reducing the opportunity for tumour cells to be missed, and reducing the chances of damaging healthy tissue.

Carina’s CEO, Dr Deborah Rathjen, commented: "This collaboration with AdAlta gives us the capability to generate bi-specific CAR molecules and then next-generation CAR-T cell products with enhanced cancer targeting and efficacy – something we are very excited about. The collaboration is off to a great start with Carina already having successfully inserted an AdAlta i-body into a CAR-T cell with functional cancer killing capability."

Carina and AdAlta will jointly fund pre-clinical proof-of-concept studies in mouse tumour models and will jointly own products emerging from the collaboration.

Aileron Therapeutics Presents Initial Findings from Ongoing Healthy Volunteer Study of ALRN-6924 at ISEH 50th Annual Scientific Meeting

On August 27, 2021 Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology company focused on fundamentally transforming the experience of chemotherapy for cancer patients, reported a poster presentation showcasing initial findings from its ongoing study of ALRN-6924 in healthy volunteers at the International Society for Experimental Hematology (ISEH) 50th Annual Scientific Meeting, which is currently underway (Press release, Aileron Therapeutics, AUG 27, 2021, View Source [SID1234586958]). The initial findings demonstrated that a 0.3 mg/kg dose of ALRN-6924 has been very well tolerated and resulted in p53-mediated induction of the cell cycle inhibitor p21 in healthy, normal bone marrow cells without concurrent induction of apoptosis. The poster can be viewed on Aileron’s website here.

"We’re pleased to present our first human data demonstrating ALRN-6924’s mechanism of action, namely, p53-mediated induction of p21 in healthy, normal cells without concurrently inducing apoptosis," said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer of Aileron. "We believe these data validate our previously presented preclinical mechanism of action results for ALRN-6924 and also support the robust chemoprotective effect ALRN-6924 demonstrated against multiple chemotherapy-induced bone marrow toxicities in our Phase 1b trial in patients with p53-mutated small-cell lung cancer (SCLC). We look forward to presenting additional data from the ongoing healthy volunteer study in the future and evaluating clinical translation of these findings in our ongoing randomized, double-blind, placebo-controlled trial of ALRN-6924 in patients with p53-mutated NSCLC."

The healthy volunteer study is designed to characterize the time to onset, magnitude and duration of p21-induced cell cycle arrest in human bone marrow relative to ALRN-6924 administration. The ultimate aim of the study is to develop a universal dosing regimen for ALRN-6924 for use as a selective chemoprotective agent across a range of chemotherapies and p53-mutant tumor indications.

Aileron is currently evaluating ALRN-6924 in a Phase 1b randomized, double-blind, placebo-controlled trial of ALRN-6924 in patients with advanced p53-mutated NSCLC undergoing treatment with first-line carboplatin plus pemetrexed with or without immune checkpoint inhibitors.

In October 2020, Aileron presented data from its now completed Phase 1b clinical trial of ALRN-6924 in SCLC, demonstrating clinical proof-of-concept that treatment with ALRN-6924 resulted in a protective effect against neutropenia, thrombocytopenia and anemia in patients with p53-mutated SCLC treated with topotecan. Aileron will present final data from the Phase 1b SCLC trial and additional data from the healthy volunteer study at the upcoming European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, being held September 16-21, 2021.

OSE Immunotherapeutics and ARCAGY-GINECO Announce First Patient Randomized in Phase 2 Clinical Trial Evaluating Tedopi®

On August 26, 2021 OSE Immunotherapeutics and the French cooperative group ARCAGY-GINECO reported that the first patient has been randomized in the Phase 2 clinical trial evaluating Tedopi alone and in combination with MSD’s Keytruda (pembrolizumab) as maintenance treatment in patients with recurrent ovarian cancer after chemotherapy (the TEDOVA trial) (Press release, OSE Immunotherapeutics, AUG 26, 2021, View Source [SID1234646975]).

The three arm TEDOVA study aims at evaluating the neo-epitope-based vaccine Tedopi as a maintenance treatment, alone or in combination with anti-PD-1 immune checkpoint inhibitor Keytruda, versus best supportive care in patients with first or second platinum-sensitive recurrent ovarian cancer with controlled disease after platinum-based chemotherapy and who have already received both bevacizumab and a PARP (Poly ADP-Ribose Polymerase) inhibitor.

Dr Alexandra Leary, Chief Investigator of TEDOVA study from Gustave Roussy cancer center, comments: "We are very pleased to announce enrolment of the first patient in TEDOVA, the first trial evaluating an innovative maintenance strategy for patients in first or second platinum sensitive relapse post-PARP inhibitor and bevacizumab. We look forward to evaluating this therapeutic option for women with ovarian cancer and a strong unmet medical need ".

Patients with ovarian cancer do not respond to checkpoint inhibitors (ICI) alone because these tumors are ‘immune cold’. The objective of TEDOVA is to turn ovarian cancer into an ‘immune hot’ tumor using a combination of tumor associated neo-epitopes that have been optimized to break immunological self-tolerance.

This Phase 2 trial, sponsored by the "Association de Recherche sur les CAncers dont GYnécologiques (ARCAGY-GINECO)" on behalf of GINECO, is designed to enroll 180 patients and will be conducted at approximately 30 sites in France and around 12 sites in Germany and Belgium.

Alexis Peyroles, Chief Executive Officer of OSE Immunotherapeutics, adds: "Having the first patient enrolled by our oncology group partner marks a significant milestone in Tedopi’s development by exploring its impact in an additional oncology indication. We are expecting first results on the potential of such an innovative PD-1 targeted checkpoint combination strategy at the beginning of 2025".

ABOUT OVARIAN CANCER
Worldwide, ovarian cancer is the seventh most common cancer and the eighth leading cause of cancer death in women. The five-year survival rate for ovarian cancer worldwide is 30-40%. In 2018, there were nearly 300,000 new cases diagnosed. Once the first relapse has occurred, ovarian cancer is managed as a chronic disease, requiring iterative lines of platinum-based chemotherapy. After 6 cycles, chemotherapy is stopped and one of the major priorities is to extend "chemotherapy-free" intervals for the patients by proposing maintenance strategies with targeted therapies (PARP inhibitors or bevacizumab). By the time patients with ovarian cancer present with first or second relapse, they will have received BOTH a PARP inhibitor and bevacizumab, thus patients progressing post-PARP inhibitors and bevacizumab represent an area of unmet medical need, they are offered chemotherapy alone with no maintenance strategy. The TEDOVA trial focuses on these women

Oncology One announces new drug discovery project with Children’s Cancer

On August 21, 2021 Oncology One reported a new partnership with Children’s Cancer Institute to develop new drugs for the treatment of childhood solid tumours (Press release, Oncology One, AUG 26, 2021, View Source [SID1234629325]).

The partnership is focused on the development of novel small molecule drugs to treat neuroblastoma, a type of tumour that forms in the adrenal glands (above the kidney), or near the spine, chest, neck, or pelvis.

The chance of a child developing neuroblastoma is approximately 1 in 100,000 and it is the most prevalent extracranial solid tumour in children under five years old. Neuroblastoma is a serious condition with limited effective treatment options and accounts for 15% of all childhood cancer deaths in Australia. There is an urgent and unmet need for improved therapeutics to treat this cancer.

The project will be run in collaboration with Children’s Cancer Institute’s new childhood disease-focused drug discovery initiative, THerapeutic INnovations for Kids (THINK), and the project is based on the research of Associate Professor Tao Liu, head of the Gene Dysregulation Group also based at the Institute.

Associate Professor Tao Liu’s work has identified a novel protein target that drives tumour growth and is a critical regulator of gene expression in neuroblastoma. The collaboration will initially seek to identify small molecule compounds that inhibit the tumour-driving biological activity of the target. This work involves the screening of hundreds of thousands of compounds using specialised assays developed specifically for this novel target.

Oncology One CEO, Dr Joanne Boag, said: "There is a real lack of funding in Australia to undertake the translational work we are doing in partnership with Children’s Cancer Institute. We are really excited to be working with them on this project, the next step in building on their quality research outcomes towards potential new therapies."

If successful, further work will be needed to develop these compounds towards a ‘lead candidate’ and then a ‘clinical candidate’ that would become an investigational new drug and enter clinical trials.

Chair of the Oncology One Scientific Advisory Board, Dr Ian Street, said: "This project, if successful could dramatically improve treatment outcomes for children with neuroblastoma, and potentially other paediatric and adult cancers as well. This is an early-stage drug discovery project, the first step in the journey of translating a "great Idea" from fundamental research into a new drug for treating patients. This gap is often referred to as the "valley of death" and many commercial investors shy away from early-stage projects. At Oncology One we refer to it as the "Valley of Opportunity" and have developed a unique commercial strategy to partner with research institutions to move these opportunities forward."

Children’s Cancer Institute Executive Director, Professor Michelle Haber AM, said: "We are delighted to be partnering with Oncology One to translate our research from target discovery to drug development. At Children’s Cancer Institute, we are passionate about curing childhood cancer. Cancer kills three children every week in Australia, and of those who survive, 70% will suffer long-term side effects from their non-targeted and aggressive treatments. There is therefore a clear unmet need for new targeted therapies to be specifically designed to treat childhood cancers, and we look forward to working towards this goal with Oncology One."

APS Announces Successful Completion of Pre-IND Meeting With FDA

On August 26, 2021 APS reported that successfully completed the Pre-IND meeting with the US Food and Drug Administration (FDA) (Press release, Applied Pharmaceutical Science, AUG 26, 2021, View Source [SID1234613103]). APS plans to conduct a clinical trial of next-generation RET inhibitor APS03118 in patients not limited by tumor type, under the US IND . The patients with RET-positive non-small cell lung cancer, thyroid cancer or other solid tumors that develop resistance to RET inhibitors will be recruited in the study to investigate the safety and efficacy of APS03118. At the meeting, the FDA provided feedback regarding APS’s planned initiation of clinical trials under a U.S. IND for its lead next-generation RET inhibitor APS03118.