On March 3, 2020 Senti Biosciences, Inc., the gene circuit company focused on outsmarting complex diseases with intelligent medicines, reported that Jose Iglesias, M.D., has joined the company as Chief Medical Officer (CMO) (Press release, Senti Biosciences, MAR 3, 2020, View Source [SID1234555145]). In this position, Dr. Iglesias will lead the clinical development of Senti’s next-generation cell and gene therapy product candidates focused on the treatment of solid and liquid tumors.

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"We are excited to have Jose join our team as chief medical officer," said Tim Lu, CEO of Senti Biosciences. "He brings a wealth of experience in oncology clinical development to Senti in that he has designed and implemented clinical trials of novel cancer therapies across all development phases. This expertise will be critical as we advance our SENTI-101 program into the clinic later this year, in addition to our upcoming pipeline programs."

"I’m thrilled to be joining such a talented and diverse team at Senti Biosciences, a company that is pioneering the development of gene circuit-based therapies," said Dr. Iglesias. "I look forward to stewarding these novel therapies through the clinic and into approved treatments for cancer patients with high unmet needs."

Dr. Iglesias has more than three decades of global clinical development experience in the biopharmaceutical industry. He has previously held multiple CMO and clinical development leadership roles at companies such as Abraxis, Celgene, Eli Lilly, Boston Biomedical, Apobiologix, Biothera Pharmaceuticals and Bionomics. In these roles, he has led the clinical development of biologics and small molecules in both solid and liquid tumors, bringing extensive experience to Senti’s growing oncology pipeline. While at Abraxis and Celgene, Dr. Iglesias designed and implemented the Phase 3 development of ABRAXANE for the treatment of metastatic pancreatic, breast and non-small cell lung cancers.

About Senti Biosciences’ SENTI-101 Program

Senti’s gene circuit platform enables the programming of any cell and gene therapy modality, including immune cells, stem cells and viral vectors. Senti’s SENTI-101 program uses tumor-homing allogeneic cells as a drug delivery vehicle to achieve localized, combinatorial expression of two cytokines, IL-12 and IL-21. This pair of cytokines activates a multifactorial immune response against solid tumors, and turns immunologically cold tumors hot. In the second half of 2020, Senti intends to submit an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for the initiation of a first-in-human clinical study of SENTI-101 in patients with ovarian cancer.

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.

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]):

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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

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.

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"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.

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.

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"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.