On September 22, 2020 Jasper Therapeutics, Inc., a biotechnology company focused on hematopoietic cell transplant therapies, reported that the first patient has been dosed in a multicenter Phase 1 clinical trial of JSP191, a first-in-class humanized monoclonal antibody (Press release, Jasper Therapeutics, SEP 22, 2020, View Source [SID1234565496]). The trial is evaluating JSP191 as a conditioning agent in patients with two types of hematologic disorders – myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) – who are undergoing blood or hematopoietic cell transplantation.

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Hematopoietic cell transplantation offers the only potentially curative therapy for MDS and many forms of AML. However, standard-of-care conditioning regimens given prior to blood cell transplantation are highly toxic and associated with increased rates of relapse due to the persistence of disease-causing hematopoietic stem cells and insufficient graft versus leukemia effect.

"JSP191 is a very targeted therapy that causes the hematopoietic stem cells that occupy the bone marrow in MDS/AML patients to be depleted, leaving room for the transplanted stem cells to engraft," said Andrew Artz, M.D., M.S., co-principal investigator of the Phase 1 trial and Associate Clinical Professor, Department of Hematology & Hematopoietic Cell Transplantation; Director, Program for Aging and Blood Cancers; Deputy Director, Center for Cancer and Aging, City of Hope Comprehensive Cancer Center. "We look forward to further evaluating JSP191 to determine its potential as a biologic conditioning regimen."

The trial is currently open for enrollment at City of Hope Comprehensive Cancer Center and Stanford University; additional clinical trial sites in the United States will initiate enrollment in the coming weeks.

"As an anti-CD117 antibody, JSP191 is the first targeted antibody of its kind to be evaluated as a conditioning agent in patients with hematologic malignancies – an area of great unmet medical need," said Kevin N. Heller, M.D., Head of Research and Development at Jasper Therapeutics. "We have seen preclinical proof-of-concept with JSP191 as a single agent in MDS/AML, and this study may provide clinical proof-of-concept, which will support advancing the compound as an antibody-based alternative to chemotherapy- or radiation-based conditioning regimens to prepare patients for a stem cell transplant or gene therapy."

He added, "With the Phase 1 trial in hematologic disorders now underway, we are currently evaluating JSP191 in the second of a long line of indications we plan to seek. This is just the beginning, as we plan to conduct additional studies in pursuit of our goal of curing more patients with cancer and other life-threatening diseases."

About the Phase 1 Study Design

The open-label, multicenter Phase 1 study (JSP-CP-003) is designed to evaluate the safety, tolerability and efficacy of adding JSP191, an anti-CD117 monoclonal antibody, to the standard conditioning regimen of low-dose radiation and fludarabine (a chemotherapy agent) in adults with MDS or AML undergoing hematopoietic cell transplantation. Three different doses of JSP191 will be assessed for dose-limiting toxicities. The primary outcome measure is the safety and tolerability of JSP191 as a conditioning regimen up to one year following a donor cell transplant.

About MDS and AML

Myelodysplastic syndromes (MDS) are a group of disorders in which immature blood-forming cells in the bone marrow become abnormal and do not make new blood cells or make defective blood cells, leading to low numbers of normal blood cells, especially red blood cells.1 In about one in three patients, MDS can progress to acute myeloid leukemia (AML), a rapidly progressing cancer of the bone marrow cells.1 Both are diseases of the elderly with high mortality. Each year, about 5,000 patients with MDS and 8,000 people with AML in the G7 countries receive hematopoietic stem cell transplants. These transplants are curative but are underused due to the toxicity of the current high-intensity conditioning regimen, which includes the chemotherapy agents busulfan and fludarabine.

About JSP191

JSP191 (formerly AMG 191) is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that clears hematopoietic stem cells from bone marrow. JSP191 binds to human CD117, a receptor for stem cell factor (SCF) that is expressed on the surface of hematopoietic stem and progenitor cells. The interaction of SCF and CD117 is required for stem cells to survive. JSP191 blocks SCF from binding to CD117 and disrupts critical survival signals, causing the stem cells to undergo cell death and creating an empty space in the bone marrow for donor or gene-corrected transplanted stem cells to engraft.

Preclinical studies have shown that JSP191 as a single agent safely depletes normal and diseased hematopoietic stem cells, including in an animal model of myelodysplastic syndromes (MDS). This creates the space needed for transplanted normal donor or gene-corrected hematopoietic stem cells to successfully engraft in the host bone marrow. To date, JSP191 has been evaluated in more than 80 healthy volunteers and patients.

JSP191 is currently being evaluated as a sole conditioning agent in a Phase 1/2 dose-escalation and expansion trial to achieve donor stem cell engraftment in patients undergoing hematopoietic cell transplant for severe combined immunodeficiency (SCID), which is potentially curable only by this type of treatment. JSP191 is also being evaluated in a Phase 1 study in patients with MDS or acute myeloid leukemia (AML) who are receiving hematopoietic cell transplant. For more information about the design of these clinical trials, visit www.clinicaltrials.gov (NCT02963064 and NCT04429191). Additional studies are planned to advance JSP191 as a conditioning agent for patients with other rare and ultra-rare monogenic disorders and autoimmune diseases.

On September 22, 2020 Genosity, Inc., an innovative biotechnology company that provides comprehensive software and technical solutions to enable precision medicine reported that it has entered into a strategic collaboration with Personal Genome Diagnostics Inc. (PGDx), one of the leading companies in cancer genomics, that recently received market clearance from the U.S. Food and Drug Administration (FDA) for PGDx elio tissue complete, a comprehensive diagnostic kit for genomic profiling of cancer (Press release, Genosity, SEP 22, 2020, View Source [SID1234565495]).

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Under the terms of this non-exclusive partnership agreement, PGDx and Genosity will collaborate to co-market their respective services and products. As part of the agreement, Genosity will incorporate the PGDx elio tissue complete assay into its software platform and professional consulting services. PGDx will co-market Genosity’s Integrated Genomic Toolkit (IGT) designed to support integration of next generation sequencing based testing into precision medicine programs across biopharmaceuticals, commercial laboratories, and health systems.

Genosity’s IGT SaaS solution is a HIPAA-compliant platform that supports end to end workflows for clinical next generation sequencing (NGS) along with EMR integration for return of results and data analytics. IGT is a modular platform built with independent but integrated applications, including Gateway, LIMS, Pipeline, Case Analyzer, and Cortex. Genosity will pre-configure the LIMS workflows for PGDx elio tissue complete assay to enable easier and faster implementation of wet-lab workflows with appropriate quality monitoring. In addition, Genosity will integrate its Case Analyzer application with PGDx’s bioinformatic pipeline to enable labs to integrate assay results into physician centric reports. Genosity’s Cortex organizes the genomic and clinical data in a knowledgebase to enable population-level analysis and cohort identification to support research collaborations.

"Genosity has established a novel software and technical approach that allows laboratories to more effectively implement genetic testing," said Dr. Marc D. Grodman, MD, co-founder and chief executive officer of Genosity."PGDx has gained approval for an important assay to help improve the outcomes of cancer patients. We see informatics as an essential component to allow greater adoption of genetic testing and we appreciate working with a partner like PGDx who is bringing best of breed testing to laboratories globally."

"PGDx elio tissue complete is a first of its kind FDA cleared kit to enable any molecular lab to perform comprehensive tumor profiling. Every lab is unique, but the importance of data integration is consistent in maximizing the value of NGS data in improving clinical care," said Megan Bailey, Chief Executive Officer of PGDx. "We’ve built the PGDx elio software to be flexible in meeting the integration needs of any lab. The addition of Genosity provides labs an option for a comprehensive solution, built from the ground up for the needs of molecular testing and NGS data."

On September 22, 2020 Promega Corporation reported its intent to develop the Promega OncoMate microsatellite instability (MSI) Assay as a companion diagnostic test for retifanlimab, Incyte’s anti-PD-1 drug candidate, in endometrial cancer (Press release, Promega, SEP 22, 2020, View Source [SID1234565494]). Financial terms of the global agreement with Incyte were not disclosed.

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Microsatellite instability-high (MSI-H) is a key feature of Lynch syndrome tumors, indicative of a germline mutation in mismatch repair genes, but can also arise sporadically. It occurs frequently in endometrial cancer. The importance of the MSI-H biomarker has been further emphasized since the 2015 finding that MSI-H tumors have a prolonged and durable response to PD-1 inhibitors.

"This announcement further underscores Promega’s dedication to advance the promise of MSI technology globally, building on over 20 years of expertise in this field," said Heather Tomlinson, Director of Clinical Diagnostics at Promega Corporation.

Promega and Incyte intend to work together in the future to develop the Promega OncoMate MSI Assay as a companion diagnostic in other markets.

The OncoMate MSI Assay received CE marking in Europe earlier this year. Promega MSI technology is one of the leading standard tests for MSI status detection in research laboratories and achieved innovation status and priority review by the National Medical Products Administration (NMPA) in China. It has been used extensively in clinical research for more than 15 years and is supported by more than 140 peer-reviewed publications. Promega intends to seek regulatory clearance for OncoMate MSI in the United States and China.

To learn more about Promega MSI testing, visit: www.promega.com/MSI

On September 22, 2020 Lantern Pharma (Nasdaq: LTRN), a clinical-stage biopharma company using its proprietary RADR artificial intelligence ("A.I.") platform to improve drug discovery & development and identify patients who will benefit from its targeted oncology therapeutics, reported a collaboration and research agreement with Fox Chase Cancer Center for the further development of Lantern’s LP-184 in pancreatic cancer (Press release, Lantern Pharma, SEP 22, 2020, View Source [SID1234565493]). Based in Philadelphia, Fox Chase is a leading research center for pancreatic cancers and one of the four original cancer centers to receive comprehensive cancer center designation from the National Cancer Institute (NCI).

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The Fox Chase collaboration will focus on advancing the targeted use of LP-184 in molecularly-defined sub-types of pancreatic cancer. The goal of the collaboration is to create a more biologically relevant and robust gene signature in preparation for future clinical trials, enabling pancreatic cancer patients to potentially benefit from a more effective and personalized cancer therapy.

"Collaborations with world-leading cancer centers are an essential part of our strategy to rapidly advance the insights driving our therapeutic programs and grow our RADR A.I. platform by adding millions of new, unique, and proprietary data points," said Panna Sharma, CEO of Lantern Pharma. "This relationship with Fox Chase will allow us to use state-of-the-art models and biological methods to add more physiologically relevant data and insights into the mechanisms of LP-184, and will further shape our algorithms for how certain compounds interact with specific tumor types. The unique insights we gain will equip Lantern with critical advantages in our aim of accelerating LP-184’s path to clinical trials and ultimately commercialization, while saving millions of dollars in development costs. This data-enabled, and biomarker-based approach has the potential to meaningfully bend the cost curve of cancer drug development and help bring personalized cancer therapies to patients with reduced economic burden, and greater efficacy."

The research will be led by Igor Astsaturov, MD, Ph.D., an internationally-recognized researcher in gastrointestinal cancers at the Molecular Therapeutics Program at Fox Chase where he specializes in investigating signaling pathways that inform the choice of biomarkers and innovative therapy combinations in clinical trials. Dr. Astsaturov is known for his research in a number of cancer indications spanning pancreatic, stomach, liver, and several others, as well as his belief that each individual cancer patient will soon be defined by the molecular makeup of their cancer cells.

LP-184 is a DNA-damaging small molecule drug candidate currently in preclinical development for certain genomically defined solid tumors, including pancreatic cancer. As a next-generation alkylating agent that preferentially damages DNA in cancer cells that overexpress certain biomarkers, LP-184 has the potential to be used as both monotherapy as well as a synergistic agent in combination with other drugs.

"We are very pleased to partner with Lantern Pharma in establishing a collaboration that will play an important role in our research," said Igor Astsaturov, MD, PhD, and Associate Professor, Department of Hematology/Oncology at Fox Chase. "Our advanced research approach using patient-derived cancer models will provide us with critical insights into the efficacy of LP-184 in pancreatic cancers. We look forward to sharing these results with the broader scientific community and hopefully bringing this drug to cancer patients that can best benefit from this compound."

The research program is at the forefront of translational cancer medicine and will use patient-derived cancers that are grown in the lab and transformed into physiologically relevant 3D organoids and PDx models. This innovative approach allows researchers to more precisely understand the biology of what actually happens inside the cancer tumor, which will more accurately establish the precise biomarker signatures and help provide data-driven insight into additional mechanisms that can be leveraged in the fight against pancreatic cancer.

Among several objectives, the research will determine whether the overexpression of the gene PTGR1, a biomarker that has been linked to cancer cell proliferation, will indicate heightened sensitivity to LP-184 and a more favorable response rate and efficacy as compared to standard of care agents. LP-184 has been advanced using Lantern’s proprietary RADR A.I. platform that leverages over 500 million data points, machine learning, genomics, and computational biology to accelerate the discovery of potential mechanisms of action, and genomic and biomarker signatures that correlate to drug response in cancer patients.

Although significant recent advances have been made in the use of targeted and biomarker-based therapies in cancer, pancreatic cancer remains an area that has not experienced significant improvement in patient outcomes. The overall five-year survival rate for pancreatic cancer across all stages remains at only 10.0% in the US and 8.2% globally, and pancreatic cancer is expected to become the 2nd leading cause of cancer death in the USA in 2020 behind lung cancer according to the National Cancer Institute’s SEER Stat Database.

On September 22, 2020 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported positive top-line results from the Phase 1 EXPLORER and Phase 2 PATHFINDER clinical trials of AYVAKIT (avapritinib) in patients with advanced systemic mastocytosis (SM) (Press release, Blueprint Medicines, SEP 22, 2020, View Source [SID1234565492]). Consistent with previously reported EXPLORER trial results, the registrational data for AYVAKIT showed profound reductions in mast cell burden, high overall response and complete remission rates, and durable clinical benefit, including prolonged median overall survival (OS). AYVAKIT was generally well-tolerated, with an improved safety profile at the 200 mg once daily (QD) dose. Based on these data, Blueprint Medicines plans to submit a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for AYVAKIT for the treatment of advanced SM in the fourth quarter of 2020.

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SM is a rare, debilitating disease driven by the KIT D816V mutation in nearly all patients. Uncontrolled mast cell proliferation and activation may lead to life-threatening complications across the SM patient population. In advanced SM subtypes, the median OS is approximately 3.5 years in aggressive SM (ASM), approximately two years in SM with an associated hematologic neoplasm (SM-AHN) and less than six months in mast cell leukemia (MCL). AYVAKIT, an investigational precision therapy for the treatment of SM, is the only highly potent KIT D816V inhibitor that has been clinically validated in SM.

"New treatment options are urgently needed to address mast cell infiltration associated with advanced systemic mastocytosis, which often leads to extensive organ damage and poor survival despite existing therapeutic interventions," said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. "These top-line data underscore the transformative impact shown by AYVAKIT, with patients achieving profound reductions in mast cell burden, durable responses that deepen over time and prolonged overall survival relative to historical outcomes. Based on these positive results, we aim to rapidly bring this promising treatment to patients, with the goal of improving and extending their lives beyond what is possible with currently available therapy."

Top-line EXPLORER and PATHFINDER Trial Data

Across both trials, 85 patients were evaluable for response per the modified IWG-MRT-ECNM criteria (IWG criteria), including 44 patients treated with a starting dose of 200 mg QD. Top-line results are being reported as of a data cutoff date of May 27, 2020 in the EXPLORER trial and a data cutoff date of June 23, 2020 in the PATHFINDER trial, with response assessments per central review completed in September 2020. Registrational endpoints are overall response rate (ORR) and duration of response (DOR), based on central review. ORR was defined as complete remission with full or partial recovery of peripheral blood counts (CR/CRh), partial remission or clinical improvement. All reported clinical responses were confirmed.

In the EXPLORER trial, 53 patients were response evaluable, with a median follow-up of 27.3 months. In EXPLORER, the ORR was 76 percent (95% CI: 62%, 86%), and 36 percent of patients had a CR/CRh. The median DOR was 38.3 months (95% CI: 21.7 months, not estimable). The median OS was not estimable (95% CI: 46.9 months, not estimable).

In a pre-specified interim analysis from the PATHFINDER trial, 32 patients were response evaluable, with a median follow-up of 10.4 months. The ORR was 75 percent (95% CI: 57%, 89%), and 19 percent of patients had a CR/CRh. In addition, the data showed that responses are continuing to deepen over time, at a rate consistent with the EXPLORER trial. The median DOR was not estimable (95% CI: not estimable, not estimable), and OS was not assessed due to the length of time patients have been enrolled in PATHFINDER. The top-line PATHFINDER results were based on a pre-planned analysis designed to assess the superiority of AYVAKIT versus the ORR per IWG criteria previously reported for the multi-kinase inhibitor midostaurin. The interim analysis achieved its primary endpoint with a p-value of p=0.0000000016.

In a pooled efficacy analysis from the 200 mg QD dose group, 44 patients were response evaluable, with a median follow-up of 10.4 months. In this group, the ORR was 68 percent, and 18 percent of patients had a CR/CRh.

Safety data were consistent with previously reported results, and no new signals were observed. AYVAKIT was generally well-tolerated with most adverse events (AEs) reported as Grade 1 or 2. In the EXPLORER and PATHFINDER trials, AYVAKIT demonstrated improved tolerability at a starting dose of 200 mg QD, compared to all doses. Across both trials, 8.1 percent of patients discontinued AYVAKIT due to treatment-related AEs.

Previously reported results from the EXPLORER trial showed that pre-existing severe thrombocytopenia, which occurs in approximately 10 to 15 percent of advanced SM patients based on Blueprint Medicines estimates, and starting doses of 300 mg QD or higher were risk factors for intracranial bleeding (ICB). Based on these data, Blueprint Medicines implemented treatment management guidelines in the EXPLORER and PATHFINDER trials, including exclusion criteria for pre-existing severe thrombocytopenia, routine platelet monitoring and dose interruption guidelines for emergent severe thrombocytopenia. In 76 EXPLORER and PATHFINDER trial patients without pre-existing severe thrombocytopenia treated at the 200 mg QD dose, two patients (2.6 percent) had ICB events. Both AEs were Grade 1 and asymptomatic. These safety data validate the clinical impact of the treatment management guidelines.

Blueprint Medicines plans to present detailed results from the EXPLORER and PATHFINDER trials at a future medical meeting.

Conference Call Information

Blueprint Medicines will host a live webcast today beginning at 8:30 a.m. ET to discuss the top-line results of AYVAKIT in advanced SM. To access the live call, please dial (855) 728-4793 (domestic) or (503) 343-6666 (international) and refer to conference ID 5338896. A webcast of the conference call will be available under "Events and Presentations" in the Investors & Media section of Blueprint Medicines’ website at View Source The archived webcast will be available on Blueprint Medicines’ website approximately two hours after the conference call and will be available for 30 days following the call.

About SM

SM is a rare disease driven by the KIT D816V mutation. Uncontrolled proliferation and activation of mast cells result in chronic, severe and often unpredictable symptoms for patients across the spectrum of SM. The vast majority of those affected have non-advanced (indolent or smoldering) SM, with debilitating symptoms that lead to a profound, negative impact on quality of life. A minority of patients have advanced SM, which encompasses a group of high-risk SM subtypes including ASM, SM-AHN and MCL. In addition to mast cell activation symptoms, advanced SM is associated with organ damage due to mast cell infiltration and poor OS.

Debilitating symptoms associated with SM, including anaphylaxis, maculopapular rash, pruritis, brain fog, fatigue and bone pain, often persist despite treatment with a number of symptomatic therapies. Patients often live in fear of attacks, have limited ability to work or perform daily activities, or isolate themselves to protect against unpredictable triggers.

Currently, there are no approved therapies that selectively inhibit D816V mutant KIT. A multi-kinase inhibitor, midostaurin, is approved for the treatment of advanced SM and has shown an ORR of 28 percent per IWG criteria, with ORR defined as complete remission, partial remission or clinical improvement.

About AYVAKIT (avapritinib)

AYVAKIT (avapritinib) is a kinase inhibitor approved by the FDA for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. For more information, visit www.AYVAKIT.com.

AYVAKIT is not approved for the treatment of any other indication, including SM, in the U.S. by the FDA or for any indication in any other jurisdiction by any other health authority.

Blueprint Medicines is developing AYVAKIT globally for the treatment of advanced and indolent SM. The FDA granted breakthrough therapy designation to AYVAKIT for the treatment of advanced SM, including the subtypes of ASM, SM-AHN and MCL.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of AYVAKIT in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for AYVAKIT in the rest of the world.

About the Clinical Development Program for AYVAKIT in Advanced SM

AYVAKIT is currently being evaluated in two ongoing, registrational clinical trials for advanced SM: the EXPLORER trial (ClinicalTrials.gov Identifier: NCT02561988) and the PATHFINDER trial (ClinicalTrials.gov Identifier: NCT03580655).

The EXPLORER trial is an open-label, single-arm trial designed to identify the recommended Phase 2 dose and demonstrate proof-of-concept in patients with advanced SM. Key trial endpoints include ORR, DOR, quantitative measures of mast cell burden, patient-reported outcomes and safety. The EXPLORER trial has completed patient enrollment.

The PATHFINDER trial is an open-label, single-arm registration-enabling trial designed to confirm the clinical activity of AYVAKIT in patients with advanced SM. Key trial endpoints include ORR, DOR, quantitative measures of mast cell burden, patient-reported outcomes and safety. Patient enrollment is ongoing in the PATHFINDER trial.