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Shattuck Labs Announces Initiation of Phase 1 Clinical Trial of SL-172154 (SIRPα-Fc-CD40L) for the Treatment of Ovarian Cancer

On August 31, 2020 Shattuck Labs, Inc. ("Shattuck"), an innovative clinical-stage biotechnology company advancing its proprietary Agonist Redirected Checkpoint (ARC) platform to develop an entirely new class of biologic medicine for the treatment of cancer and autoimmune disease, reported initiation of a Phase 1 clinical trial of its compound SL-172154 (SIRPα-Fc-CD40L), a bi-functional fusion protein that simultaneously blocks the CD47/SIRPα checkpoint and activates the tumor necrosis factor (TNF) costimulatory receptor CD40 (Press release, Shattuck Labs, AUG 31, 2020, View Source [SID1234564192]).

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"SL-172154 is our lead wholly owned product candidate and a potentially best-in-class CD47 checkpoint inhibitor, a recently clinically validated target for cancer immunotherapy," said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. "In preclinical studies, SL-172154 demonstrated superior anti-tumor activity as compared to either CD47- or CD40-targeted antibodies, either alone or in combination. Based on its ability to simultaneously block the CD47/SIRPα checkpoint and activate the CD40 costimulatory receptor, we believe SL-172154 offers a promising approach to treating patients with ovarian cancer and a range of other cancer types."

The Phase 1 clinical trial is a multicenter, open-label, dose-escalation study. The study will evaluate the safety, tolerability, pharmacokinetics, anti-tumor, and pharmacodynamic effects of SL-172154. Initial clinical data from the trial are expected in the second half of 2021. In addition, Shattuck plans to evaluate SL-172154 in combination with other therapeutic agents in specific cancers.

"CD47/SIRPα checkpoint blocking therapeutics have emerged as promising immuno-oncology therapies. We are incredibly excited to have now initiated this clinical trial evaluating SL-172154 in patients with ovarian cancer, where there remains a high unmet need for effective new therapies," said Lini Pandite, M.D., Chief Medical Officer of Shattuck.

About SL-172154

SL-172154 is a bi-functional fusion protein designed to simultaneously inhibit the CD47/SIRPα checkpoint and activate the TNF costimulatory receptor CD40. In preclinical studies, SL-172154 demonstrated the ability to bridge the innate and adaptive immune response by simultaneously blocking the CD47 macrophage "don’t eat me" signal and agonizing CD40 to induce a T cell-mediated immune response, or "eat me" signal.

VelosBio Announces FDA Fast Track and Orphan Drug Designations for VLS-101 in Patients with Mantle Cell Lymphoma

On August 31, 2020 VelosBio Inc. ("VelosBio"), a clinical-stage biopharmaceutical company committed to developing novel, first-in-class cancer therapies targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), reported that the U.S. Food and Drug Administration (FDA) has granted the company Fast Track and Orphan Drug designation for VLS-101 for the treatment of patients with mantle cell lymphoma (MCL) (Press release, VelosBio, AUG 31, 2020, View Source [SID1234564191]). VLS-101 is a ROR1-directed antibody-drug conjugate (ADC) that is currently being studied in a first-in-human Phase 1 clinical trial in patients with relapsed or refractory hematologic cancers.

FDA Fast Track designation is a program designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need, with the goal of getting important new drugs to patients earlier. Fast Track designation also confers important benefits to the sponsor, including potential eligibility for Priority Review of a New Drug Application, if relevant criteria are met.

The FDA Office of Orphan Drug Products grants Orphan Drug status to support the development of medicines for underserved patient populations, or rare disorders, that affect fewer than 200,000 people in the U.S. Orphan Drug designation provides to VelosBio certain benefits, including market exclusivity upon regulatory approval if received, exemption from FDA application fees, and tax credits for qualified clinical trials.

"We are pleased to receive FDA Fast Track and Orphan Drug designation for VLS-101 in mantle cell lymphoma, which is a significant milestone for VelosBio as we continue to advance our pipeline of ROR1-directed therapeutics," said Dave Johnson, Chief Executive Officer, VelosBio. "We look forward to working closely with the FDA to advance our investigational therapeutic and believe VLS-101 could be an important new treatment option for patients with mantle cell lymphoma."

Mantle cell lymphoma is an aggressive, rare form of non-Hodgkin lymphoma (NHL). MCL is more common in men than in women, and it most often appears in people older than 60. When MCL is diagnosed, it is usually widespread in the lymph nodes, bone marrow, and often the spleen.

Magenta Therapeutics Announced It Will Present Clinical and Pre-Clinical Data from Across Immune and Blood System Reset Portfolio at European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting

On August 31, 2020 Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplant to more patients, reported that data across the portfolio will be presented at the European Society for Blood and Marrow Transplantation (EBMT) annual meeting, held August 29 to September 1, 2020 (Press release, Magenta Therapeutics, AUG 31, 2020, View Source [SID1234564190]).

"Our presentations at EBMT showcase Magenta’s integrated approach towards bringing the curative power of blood and immune system reset through stem cell transplant to more patients and across more therapeutic areas," said John Davis Jr., M.D., M.P.H., M.S., Head of Research & Development and Chief Medical Officer, Magenta Therapeutics. "We are making significant strides towards expanding eligibility and improving patient outcomes given the far-reaching potential of our programs. We are relentlessly focused on progressing our programs forward and further into the clinic and are encouraged by our steady progress. We look forward to our continued momentum across our pipeline."

All posters will be available to view on the EBMT website beginning Saturday, August 29 at 6:30am EDT / 12:30pm CET. Visitors can view the posters by accessing the Scientific Programme and selecting "ePoster viewing."

Clinical Data from MGTA-145 First-Line Stem Cell Mobilization Program:

Magenta is developing MGTA-145 as the new first-line standard of care for stem cell mobilization in a broad range of diseases, including autoimmune diseases, blood cancers and genetic diseases, such as sickle cell disease. MGTA-145, a CXCR2 agonist, works in combination with plerixafor, a CXCR4 antagonist, harnessing the physiological mechanism of stem cell mobilization to rapidly and robustly mobilize stem cells for collection and transplant.

Title: Phase 1 Clinical Study of MGTA-145 In Combination with Plerixafor Shows Rapid Single-Day Mobilization and Collection of CD34+ HSCs Without G-CSF (Abstract #B385)
Presenting Author: John DiPersio, M.D., Ph.D., Professor of Medicine and Chief of the Oncology Division, Washington University School of Medicine, St. Louis, Missouri

These data provide further confirmation that MGTA-145, in combination with plerixafor, enables the same-day mobilization and collection of highly functional hematopoietic stem cells (HSCs) for transplant. Earlier this year, Magenta completed dosing in this Phase 1 trial, achieving all primary and secondary endpoints. In the second half of 2020, the Company plans to move the MGTA-145 program into multiple Phase 2 clinical trials to include both allogeneic and autologous transplant settings across multiple diseases. These trials will evaluate mobilization and collection of functional HSCs and engraftment of these cells after transplant.

Preclinical Data from Magenta’s Antibody-Drug Conjugate Conditioning Programs

Targeted, disease-modifying antibody-drug conjugates (ADCs) are designed to selectively and rapidly remove disease-causing cells in the body and enable immune and blood system reset and long-term engraftment, without the need for aggressive chemotherapy or radiation.

MGTA-117, the clinical candidate for ADC-based conditioning for stem cell transplant and gene therapy and Magenta’s most advanced conditioning program, is on track with IND-enabling toxicology studies ongoing and progress in GMP manufacturing. Magenta expects to generate initial clinical data in 2021.

Title: A Single Dose of Short Half-Life CD117 Antibody Drug Conjugate Enables Hematopoietic Stem Cell-Based Gene Therapy in Non-Human Primates (Abstract #O076)
Presenting Author: Rahul Palchaudhuri, Ph.D., Magenta Therapeutics, Cambridge, Mass.

This collaborative study with the National Institutes of Health (NIH) demonstrates that a single dose of a tool CD117-ADC molecule in non-human primates enables successful transplant and long-term engraftment of HSCs modified with a lentiviral vector encoding the β-globin gene, the gene that causes sickle cell disease and β-thalassemia. The ADC was well tolerated with none of the significant side effects that are seen with myeloablative dosing of busulfan chemotherapy.

Title: A Novel Targeted Approach to Achieve Immune System Reset: CD45-Targeted Antibody-Drug Conjugates Ameliorate Disease in Preclinical Autoimmune Disease Models and Enable Auto HSCT (Abstract #O030)
Presenting Author: Geoff Gillard, Ph.D., Magenta Therapeutics, Cambridge, Mass.

Magenta’s CD45-ADC program targets CD45, a protein expressed on immune cells and blood stem cells, and is designed to remove the cells that cause autoimmune diseases to enable curative immune reset. Magenta has identified a lead antibody for this program and IND-enabling work on CD45-ADC is progressing in 2020.

Preclinical data in this abstract show that a single dose of CD45-ADC removed disease-causing T-cells, enabling successful immune reset to halt disease progression and was well tolerated in three models of autoimmune disease: multiple sclerosis, systemic sclerosis and inflammatory arthritis.

Title: A CD45-Targeted Antibody Drug Conjugate Enables Allogeneic Hematopoietic Stem Cell Transplantation as a Single Agent in Mice (Abstract #A174)
Presenting Author: Sharon Hyzy, M.S., Magenta Therapeutics, Cambridge, Mass.

Preclinical data in this abstract demonstrate that a single dose of CD45-ADC is fully myeloablative and enables complete chimerism in a full mismatch allogeneic hematopoietic stem cell transplant (HSCT), representing a substantial advance in establishing the potential of this targeted approach to conditioning to potently and safely enable immune reset in the allogeneic setting.

Title: High Dose Stem Cell Therapies, like MGTA-456, Enable Complete Neural and Peripheral Disease Cross-Correction Through Rapid and Robust Hematopoietic Engraftment (Abstract #A325)
Presenting Author: Kevin Goncalves, Ph.D., Magenta Therapeutics, Cambridge, Mass.

Preclinical data in this abstract demonstrate rapid and durable peripheral, central nervous system (CNS) and skeletal disease cross-correction after transplantation of a high HSC dose. Mechanistic studies demonstrated that CNS disease cross-correction was due to robust microglial engraftment in the brain. MGTA-456 led to more robust microglial engraftment in NSG mice, suggesting that MGTA-456 may lead to rapid and durable disease resolution in the central nervous system.

Repertoire Immune Medicines to Present at the Citi 15th Annual BioPharma Virtual Conference

On August 31, 2020 Repertoire Immune Medicines, a clinical-stage biotechnology company focused on decoding and deploying the immune system across multiple major diseases, reported that it will present at Citi’s 15th Annual BioPharma Virtual Conference on Tuesday, September 8, 2020 at 9:30 am ET (Press release, Repertoire Genesis, AUG 31, 2020, View Source [SID1234564189]).

Seneca Therapeutics, Inc. Licenses Tumor Endothelial Marker 8 (TEM8) to Enable Better Patient Selection for SVV-001 Therapy

On August 31, 2020 Seneca Therapeutics, Inc., a clinical-stage biopharmaceutical company dedicated to the development of oncolytic immune-therapeutics based on Seneca Valley Virus (SVV-001), reported the company has licensed TEM 8 intellectual property from Memorial Sloan Kettering Cancer Center (MSK) (Press release, Seneca Therapeutics, AUG 31, 2020, View Source [SID1234564188]). TEM8 may enable pre-screening of solid tumors to determine if SVV-001 might be effective in that patient. This discovery is based on research from Charles Rudin, MD., Ph.D. and colleagues at MSK. Researchers at MSK discovered that a protein called TEM 8 is the receptor of SVV. This discovery supports other work in the scientific field that TEM 8 is very selectively expressed on the surface of tumor cells in many solid cancer indications. Dr. Rudin and his laboratory demonstrated that the level of expression of TEM 8 and genes in the innate immune system could predict with a high degree of certainty what type of cancer cells would support SVV replication in and killing of the tumor cells. This research, originally published in 2017, will be utilized in upcoming SVV-001 clinical trials to pre-select patients that might best respond to SVV–mediated cancer therapy.

Dr. Rudin is the Sylvia Hassenfeld Professor and Chief of Thoracic Oncology at Memorial Sloan Kettering Cancer Center. Dr. Rudin and his colleagues have been investigating SVV as a novel and promising cancer immunotherapeutic since 2005. Dr. Rudin said, "I couldn’t be more pleased to see this new exciting enabling technology head toward POC Phase II trials to demonstrate that SVV is efficacious and synergistic with checkpoint inhibitors."

Dr. Paul Hallenbeck, Founder, President, and Chief Scientific Officer at Seneca Therapeutics added, "Unlike most other oncolytic viruses SVV only replicates and kills cells that express TEM 8, namely solid tumor cells. MSK’s technology should also enable the wise selection of cancer indications best able to benefit from SVV therapy and enhance the number of patients that should respond."