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EpicentRx IND Application for Second Immuno-oncology Program, a TGF-β Trap Adenovirus, Receives FDA Clearance

On March 3, 2020 EpicentRx, Inc., a clinical cancer immunotherapy company targeting both sides of the immune system to deliver cancer treatments with minimal toxicity, reported that the U.S. Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for AIM-001, an oncolytic adenovirus that is enhanced with a TGF-β (beta) trap transgene (Press release, EpicentRx, MAR 3, 2020, View Source [SID1234555144]). With a Phase 3 trial of its lead program CD47 antagonist RRx-001 for the treatment of small cell lung cancer (SCLC) already in progress, AIM-001 is EpicentRx’s second program to move into clinical testing.

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Cancer cells overexpress TGF-β, an immunosuppressive protein, to circumvent or thwart immune surveillance and cancer immunotherapy. The effect of AIM-001 is potentially three-fold: 1) it lyses and kills tumor cells, thus releasing signals to activate T-cell responses, 2) it overexpresses TGF-β trap transgene, neutralizing TGF-β and reprograming the tumor microenvironment from immunosuppressive to immunostimulatory, and 3) since TGF-β is a master regulator of fibrosis, the TGF-β trap may reduce the fibrotic stroma and enable better penetration of anticancer therapies.

"The clearance of our IND is a major milestone for EpicentRx and the first of many oncolytic adenoviruses that are planned for development," said Tony R. Reid, M.D., Ph.D., Chief Scientific Officer of EpicentRx. "Since overexpression of TGF-β is common in many different cancers and an underlying mechanism of chemo- and immunoresistance, we generated this TGF-β trap virus to concomitantly lyse tumor cells and neutralize TGF-β," Dr. Reid said.

EpicentRx anticipates that AIM-001 will not only demonstrate single agent activity but also ‘turn up the heat on cold tumors’ and, in combination with both chemotherapy and immune checkpoint therapies, yield synergistic anti-tumor responses. EpicentRx plans to begin clinical trials with AIM-001 this year.

"AIM-001 was designed to trigger in situ vaccination and to turn the injected tumor into a nidus for antigen recognition by the immune system and generation of a potent adaptive T cell response against distant tumors," stated Christopher Larson, M.D., Ph.D., head of the EpicentRx viral program.

In addition to AIM-001, EpicentRx has developed additional IP-protected oncolytic adenoviruses with the capacity to accommodate multiple transgenes and has potential applicability to a broad range of disease targets, including those that have been considered "undruggable."

As part of its broader effort to ‘release the immunosuppressive brakes’ and turn immunologically cold tumors hot, EpicentRx’s lead program RRx-001 stimulates macrophage-mediated phagocytosis and converts "treatment-resistant" tumors into "treatment-sensitive" tumors. The candidate has been evaluated in multiple clinical studies, including the ongoing Phase 3 REPLATINUM trial for the treatment of SCLC.

Having closed its $35 million series D round last year, the company is poised to complete the Phase 3 REPLATINUM trial with RRx-001 and advance its diverse oncolytic adenoviral portfolio including AIM-001.

Eureka Therapeutics Announces Upcoming Conference Presentations

On March 3, 2020 Eureka Therapeutics, Inc., a clinical stage biotechnology company developing novel T cell therapies to treat solid tumors, reported that the company is scheduled to present at the following March healthcare conferences (Press release, Eureka Therapeutics, MAR 3, 2020, View Source [SID1234555143]):

Cowen 40th Annual Health Care Conference
Title: ARTEMIS Antibody TCR T Cell Therapies for Solid Tumors
Speaker: Hanzhong Li, Ph.D., Senior Vice President of Corporate Strategy
Location: Boston Marriott Copley Place, Boston, MA
Date: Wednesday, March 4, 2020
Time: 8:30 a.m. EST

BioProcess International US West
Title: Optimizing Viral Vector Production
Speaker: Nicole Nunez, Ph.D., Process Development Scientist
Location: Santa Clara Convention Center, Santa Clara, CA
Date: Wednesday, March 11, 2020
Time: 1:05 p.m. PST

Ayala Pharmaceuticals Granted U.S. FDA Fast Track Designation for AL101 for the Treatment of Recurrent or Metastatic Adenoid Cystic Carcinoma

On March 3, 2020 Ayala Pharmaceuticals, Inc., a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare and aggressive cancers, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to AL101 for the treatment of recurrent or metastatic adenoid cystic carcinoma (ACC) (Press release, Ayala Pharmaceuticals, MAR 3, 2020, View Source [SID1234555142]). AL101, Ayala’s lead product candidate, is a potent, selective, injectable small molecule gamma secretase inhibitor (GSI) and was granted Orphan Drug Designation in May 2019 for the treatment of ACC.

"Receiving Fast Track designation from the FDA underscores the urgent need for a targeted therapy to address the devastating nature of ACC, a rare disease for which no standard drug therapy currently exists," said Roni Mamluk, Ph.D., Chief Executive Officer of Ayala. "We are pleased with the initial data from our Phase 2 ACCURACY clinical trial, demonstrating that AL101 has been well tolerated and has shown encouraging preliminary signs of activity in this extremely difficult to treat patient population. We look forward to continuing discussions with the FDA in our effort to develop a novel treatment for patients in need."

The FDA’s Fast Track program is designed to facilitate the development and expedite the review of drugs intended to treat serious or life-threatening diseases or conditions and demonstrate the potential to address unmet medical needs. The designation offers the opportunity for more frequent interactions with the FDA over the course of drug development and allows for rolling review of a New Drug Application (NDA) if relevant criteria are met.

About AL101

AL101 is an investigational small molecule GSI that is designed to potently and selectively inhibit Notch 1, 2, 3 and 4, and is currently being evaluated in the Phase 2 ACCURACY trial in patients with adenoid cystic carcinoma (ACC). AL101 is designed to inhibit the expression of Notch gene targets by blocking the final cleavage step by the gamma secretase required for Notch activation. Ayala obtained an exclusive, worldwide license to develop and commercialize AL101 from Bristol-Myers Squibb Company in November 2017.

MiNA Therapeutics Announces Initiation of Phase I Clinical Study of MTL‑CEBPA in Combination with anti-PD1 Checkpoint Inhibitor in Patients with Advanced Solid Tumours

On March 3, 2020 MiNA Therapeutics, the pioneer in RNA activation therapeutics, reported the initiation and first patient treated in TIMEPOINT, a global Phase 1/1b clinical study of MTL-CEBPA in combination with anti-PD1 checkpoint inhibitor pembrolizumab in patients with advanced solid tumours (Press release, MiNA Therapeutics, MAR 3, 2020, View Source [SID1234555141]). The study is designed to assess the safety, tolerability, pharmacology and clinical activity of MTL-CEBPA in combination with pembrolizumab in these patients. MTL-CEBPA is the first therapy to specifically up-regulate CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of myeloid cell lineage determination and differentiation. The drug candidate is also being investigated in an ongoing multi-centre Phase 1b clinical trial in patients with advanced liver cancer in combination with sorafenib.

"Initiation of the Phase I TIMEPOINT clinical trial emphasizes the continued exploration of MTL-CEBPA, the first drug candidate that targets C/EBP-α, a master regulator of immune cells that play a critical role in tumour resistance," commented Robert Habib, CEO of MiNA Therapeutics. "We are excited to take the next step and test MTL‑CEBPA in additional cancer populations in a potentially synergistic combination with an anti-PD1 checkpoint inhibitor. We look forward to collaborating with our clinical investigators in evaluating this new combination."

The TIMEPOINT study consists of a dose-escalation followed by a dose expansion. MTL‑CEBPA will be administered as an intravenous infusion once weekly in cycles of three weeks of treatment followed by one week of rest. In pre-clinical studies MTL-CEBPA has been shown to improve the anti-tumour activity of anti-PD1 checkpoint inhibition by reducing immune suppression from dysregulated myeloid cells in the tumour microenvironment.

The single agent activity of MTL-CEBPA in 39 patients with advanced liver cancer was previously presented by investigators at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress. MTL-CEBPA was found to be well tolerated, demonstrating pharmacodynamic target engagement and a reduction of suppressive immune cells in the tumour microenvironment. In addition, MTL-CEBPA demonstrated clear, synergistic activity in patients with liver cancer when also treated with sorafenib standard of care.

"MTL-CEBPA has shown real promise as a combination agent in patients with liver cancer and pre-clinical studies suggest that MTL-CEBPA may also be an attractive agent to enhance the benefits of checkpoint inhibitors," commented Professor Ruth Plummer, Clinical Professor of Experimental Medicine at the Clinical and Translational Research Institute, Newcastle University Centre for Cancer, and Chief Investigator of the study. "We are looking forward to evaluating this highly innovative combination treatment in the upcoming Phase I trial. We hope this combination could become an effective new treatment option for patients with solid tumour cancers."

About the TIMEPOINT Study

TIMEPOINT is a global Phase I/Ib clinical study in patients with solid tumour malignancies that will assess the safety and tolerability of MTL-CEBPA in combination with pembrolizumab in patients who are ineligible or resistant to standard therapies. The study has received clearance from the U.S. Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). To learn more about the TIMEPOINT clinical study, please visit our listing at clinicaltrials.gov.

About MTL-CEBPA

MTL-CEBPA is the first therapy to specifically up-regulate CCAAT/enhancer binding protein alpha (C/EBP-α), a transcription factor that acts as a master regulator of myeloid cell lineage determination and differentiation. Dysregulated myeloid cells have been implicated in several diseases and identified as a critical barrier for many therapies to induce clinical responses in solid tumour cancers. In pre-clinical studies MTL-CEBPA has been shown to improve the anti-tumour activity of cancer therapies by targeting dysregulated myeloid cells and reducing their suppression in the tumour microenvironment.

PDCline Pharma Announces the Administration of a First Patient With Its Therapeutic Cancer Vaccine Candidate (PDClung01) Targeting Non-small Cell Lung Cancer

On March 3, 2020 PDC*line Pharma, a clinical stage biotech company developing a new class of potent and scalable active immunotherapies for cancers, reported that the first patient was dosed with its innovative medicinal product candidate PDC*lung01 in a phase I/II trial in non-small cell lung cancer (NSCLC) (Press release, PDC Line Pharma, MAR 3, 2020, View Source [SID1234555139]). This patient is under the supervision of Dr. Anne Sibille, principal investigator for the Liege University Hospital (Belgium).

The objectives of the phase I/II trial (PDC-LUNG-101) are to assess the safety, tolerability, immunogenicity and preliminary clinical activity of the drug candidate, PDC*lung01, associated or not with anti-PD-1 treatment in NSCLC. A total of 62 evaluable HLA-A*02:01 positive NSCLC patients are expected in three clinical centers in Belgium and six in France.

PDC*lung01 is a cell suspension of a mix, in the same proportion, of seven active agents made of irradiated human plasmacytoïd dendritic cells (PDC*line) loaded separately with a distinct synthetic human leukocyte antigen serotype-restricted peptide (HLA-A*02:01) encoded by a tumour antigen. PDC*line is a potent professional antigen-presenting cell that is able to prime and boost the antitumor cytotoxic CD8+ T-cells in the patient’s immune system.

"We are delighted to have achieved this first important milestone in the clinical development of PDC*line Pharma with our lead cancer vaccine candidate," said Eric Halioua, president and CEO of PDC*line Pharma. "Based on preclinical studies there is a strong rationale for developing PDC*lung01 in this indication and we are currently exploring a number of additional indications, where our technology may provide potential benefit for patients."

"PDC*lung01 is an innovation in the field of cancer vaccines that appears particularly suitable for the treatment of NSCLC patients, an area where there is still a high unmet medical need," said Dr. Channa Debruyne, medical director of PDC*line Pharma.

About lung cancer
Worldwide, lung cancer is the most common malignancy for male patients and for both sexes combined (2.1 million new cases per year), and the third most common for female patients (after breast and colorectal cancers). Globally, deaths from lung cancer exceed those from any other cancer, with the number of lung-cancer-related deaths for 2018 estimated at 18.1 million; 18.4% of total cancer deaths. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, representing 80% of cases.

About PDC*line Pharma’s technology

PDC*line’s biological features provide unique advantages:

A professional antigen-presenting cell line, much more potent than conventional dendritic cells in priming and expanding antitumor-specific cytotoxic CD8+ T cells (conventional tumor antigens and neoantigens)
While allogeneic, PDC*line is not rejected by the host immune system and can be injected several times to boost the immune response
Easily produced on a large scale, with a fully mastered and simple manufacturing process (use of bioreactors with a synthetic medium without growth, differentiation or activation factors)
Easy to use: after thawing, the same off-the-shelf product is used to treat the whole target population with a cancer type expressing the target antigens
Very versatile: tumor antigens can be provided by peptide loading, mRNA transfection or retrovirus transduction of PDC*line and the target population can be extended beyond HLA-A2 (currently used as it is expressed by 50% of the Caucasian population) by using other HLAs, either already expressed by PDC*line or added by genetic modification. Moreover, new candidates can be validated for new cancer indications in a few weeks, with ex vivo testing using human peripheral blood mononuclear cells (PBMC)
Synergizes with anti-PD-1 to activate antitumor CD8 T cells