On May 13, 2019 ORIC Pharmaceuticals, a privately held, clinical-stage oncology company focused on the discovery and development of novel therapies against treatment-resistant cancers, reported the initiation of patient dosing in a Phase 1b clinical study of ORIC-101 in combination with nab-paclitaxel (marketed as Abraxane by Celgene Corporation) in patients with advanced solid tumors (Press release, ORIC Pharmaceuticals, MAY 13, 2019, View Source [SID1234536231]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Phase 1b initiation of ORIC-101 in patients with cancer represents a major milestone for ORIC," said Jacob Chacko, MD, Chief Executive Officer. "ORIC’s in-house discovery team, based on findings originating from Dr. Charles Sawyers’ laboratory, identified and developed a selective and potent oral inhibitor of the glucocorticoid receptor (GR), which has been linked to treatment resistance to multiple classes of anti-cancer therapeutics across a variety of solid tumors. Building on our recently completed study in healthy volunteers, we are looking forward to this first clinical study of ORIC-101 through which we hope to begin demonstrating the potential of ORIC-101 to benefit patients with cancer."

The Phase 1b trial is a dose finding, multi-center, open label study designed to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical efficacy of ORIC-101 combined with nab-paclitaxel in patients with advanced solid tumors. Following identification of the recommended Phase 2 dose of ORIC-101 in combination with nab-paclitaxel, ORIC intends to enroll patients into expansion cohorts in selected tumor types based upon GR levels using its proprietary immunohistochemistry assay.

Subsequent to this initial Phase 1b study of ORIC-101 in combination with nab-paclitaxel, ORIC also plans to initiate additional Phase 1b studies of ORIC-101 in combination with other anti-cancer agents, including with androgen receptor modulators in patients with advanced prostate cancer and with immunotherapy agents. Ongoing and planned clinical studies of ORIC-101 are supported by research conducted at ORIC and recent clinical studies of ORIC-101 in healthy volunteers, which demonstrated that ORIC-101 appeared to be safe and well-tolerated, with a pharmacokinetic profile sufficient for oral once-daily dosing and pharmacodynamic activity suggestive of effective target engagement.

"Despite many new anti-cancer therapies, resistance remains a significant barrier to improved outcomes in most patients with advanced cancers," said Pratik Multani, MD, Chief Medical Officer. "We are excited to evaluate the potential of ORIC-101 to overcome what we believe to be a major mechanism of resistance, overexpression of GR. This first clinical trial kicks off a robust clinical development plan to evaluate ORIC-101, the first of our programs to enter the clinic, in combination with multiple classes of anti-cancer agents across various indications that span the range of solid tumor malignancies."

Further details about the clinical study are available at ClinicalTrials.gov (NCT03928314).

On May 13, 2019 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular" or "Molecular Templates"), a clinical-stage oncology company focused on the discovery and development of the company’s proprietary engineered toxin bodies (ETBs), which are differentiated, targeted, biologic therapeutics for cancer, reported financial results for the first quarter of 2019 (Press release, Molecular Templates, MAY 13, 2019, View Source [SID1234536215]). As of March 31, 2019, Molecular’s cash and investments totaled $84 million, and is expected to fund operations into the first half of 2021.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"So far in 2019, we have made substantial progress in advancing our pipeline and platform. We now have three Phase II studies open for our lead program, MT-3724, and our HER2 ETB, MT-5111, now has an open IND and Phase I dosing will begin in 3Q," said Eric Poma, Ph.D., Molecular Templates’ Chief Executive and Scientific Officer. "At the recent American Association of Cancer Research ("AACR") Annual Meeting, preclinical data was presented that showed that our second-generation ETBs utilizing our de-immunized scaffold have improved potency, greatly improved tolerability, and potential for less frequent dosing. These improvements have been demonstrated in preclinical studies with our ETBs targeting CD38, HER2, and PD-L1, all of which are expected to generate clinical data in the next 12 months."

Company Highlights and Upcoming Milestones

Corporate

Molecular presented new data on its pipeline programs and technology platform in four posters at the AACR (Free AACR Whitepaper) Annual Meeting 2019, March 29 – Apr 3, 2019 in Atlanta, Georgia. Presentations featured data on 1) CD38-targeted ETB TAK-169, 2) CD20-targeted ETB MT-3724 in combination with chemotherapy or IMiDs, 3) PD-L1-targeted ETB for direct cell kill approach to PD-L1 expressing cancers, 4) bispecific ETBs for targeted cancer treatment.
TAK-169

Takeda and Molecular expect to file an IND and start a Phase I multiple myeloma trial in 2019 for TAK-169 (CD38 targeted ETB).
MT-3724

Molecular is conducting a Phase II monotherapy study of MT-3724 in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). This study has the potential to be pivotal. Molecular expects to provide an update on this study in 2H19.
Molecular is also conducting two Phase II studies in earlier lines of DLBCL; one with MT-3724 in combination chemotherapy (GemOx) and the other with MT-3724 in combination with Revlimid. Molecular expects to report an update on both MT-3724 combination studies with MT-3724 in 2H19.
MT-5111

Molecular announced the acceptance of its IND filing for MT-5111, its ETB targeting HER2, in April 2019. The Phase I study in patients with HER2 positive solid tumors is expected to start dosing in 3Q19. Molecular expects to report an update on this study in 2H19.
Research

Molecular expects to file an IND application for MT-6035, its ETB targeting PD-L1 (with antigen seeding), in 2H19.
Several other ETB candidates are in preclinical development, targeting both solid and hematological cancers.
Takeda Multi-Target Collaboration

Takeda and Molecular are conducting lead optimization for ETBs against two undisclosed targets selected by Takeda under the collaboration. Should Takeda exercise its option to license ETBs for both targets, Molecular would receive $25 million and would be eligible to receive up to $547 million in milestone payments and tiered royalties on sales.
Financial Results

The net loss attributable to common shareholders for the first quarter of 2019 was $6.2 million, or $0.17 per basic and diluted share. This compares with a net loss attributable to common shareholders of $8.7 million, or $0.32 per basic and diluted share, for the same period in 2018.

Revenues for the first quarter of 2019 were $7.0 million, compared to $0.5 million for the same period in 2018. Revenues for the first quarter of 2019 were comprised of revenues from collaborative research and development agreements with Takeda, and grant revenue from CPRIT. Total research and development expenses for the first quarter of 2019 were $8.5 million, compared with $6.7 million for the same period in 2018. Total general and administrative expenses for the first quarter of 2019 were $4.9 million, compared with $2.9 million for the same period in 2018.

On May 13, 2019 AngioDynamics, Inc. (NASDAQ: ANGO), a leading provider of innovative, minimally invasive medical devices for vascular access, peripheral vascular disease, and oncology, reported enrollment of the first patient in its NanoKnife Irreversible Electroporation (IRE) "Data IRE Cancer Treatment" clinical study (DIRECT) (Press release, AngioDynamics, MAY 13, 2019, View Source [SID1234536232]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The DIRECT Study supports a proposed expanded indication for the NanoKnife System in the treatment of Stage III pancreatic cancer. The first patient enrollment closely follows the United States Food and Drug Administration’s (FDA) April 1, 2019 approval of AngioDynamics’ investigational device exemption (IDE) application.

"The enrollment of our first patient soon after receiving FDA approval is a strong signal that clinicians are eager to evaluate treatment alternatives that improve the dismal prognosis for Stage III pancreatic cancer patients," said Brent Boucher, AngioDynamics Senior Vice President and General Manager of Oncology. "We look forward to confirming that our proprietary NanoKnife technology offers a compelling alternative to the current standard of care and believe that this study will provide a pivotal dataset for claims and reimbursement purposes."

AngioDynamics’ DIRECT clinical study features a comprehensive data collection strategy that will provide meaningful clinical information to healthcare professionals, support a regulatory indication for the treatment of Stage III pancreatic cancer, and facilitate reimbursement for hospitals and treating physicians. The next-generation study is classified as a Category B IDE by the FDA, which allows participating sites to obtain coverage for procedures performed in addition to any related routine costs.

"We are pleased to be the first enrolling site. The DIRECT Study represents an important milestone in the standardization of care for patients with Stage III pancreatic cancer. Our goal is to generate important data that should standardize and optimize the use of IRE in the treatment of locally advanced pancreatic cancer, significantly improving outcomes for patients with this late-stage diagnosis," said Dr. Robert C.G. Martin, Co-Principal Investigator of the DIRECT Study and Surgical Oncologist at the University of Louisville.

The DIRECT Study comprises a Randomized Controlled Trial at up to 15 sites, as well as a Real-World Evidence, next-generation registry at up to 30 sites, each with a NanoKnife System treatment arm and a control arm. AngioDynamics expects each NanoKnife arm to consist of approximately 250 patients with an equal number of control patients. The primary endpoint of the study is overall survival.

As part of the DIRECT Study, AngioDynamics launched AngioDIRECT.com to facilitate the enrollment of participants. The online platform provides patients and their families with information about pancreatic cancer and details about the study. It also features a physician locator to help prospective participants and referring healthcare professionals identify clinical study locations.

There are approximately 57,000 new cases and 46,000 estimated deaths from pancreatic cancer in the United States annually1. Total deaths due to pancreatic cancer are projected to increase dramatically to become the second leading cause of cancer-related deaths before 20302. The mortality rate is high due to the aggressive nature of the disease and lack of early warning signs, and less than 20 percent of patients are candidates for surgical resection at time of diagnosis3. Approximately 35 to 40 percent of patients will present with Stage III and 45 to 55 percent with metastatic disease3. Regardless of the stage of pancreatic cancer, it is one of the least survivable cancers, and survival rates have not improved substantially for more than forty years3. For all stages combined, the five-year relative survival rate is 8 percent and, for those with advanced disease at the time of diagnosis, the five-year survival rate remains at 3 percent3.

On May 13, 2019 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for CLR 131 in fourth line or later relapse/refractory multiple myeloma (Press release, Cellectar Biosciences, MAY 13, 2019, View Source [SID1234536216]). CLR 131 is the company’s small-molecule radiotherapeutic phospholipid drug conjugate (PDC) designed to deliver cytotoxic radiation directly and selectively to cancer cells and cancer stem cells. It is currently being evaluated in Cellectar’s ongoing CLOVER-1 Phase 2 clinical study in patients with relapsed or refractory multiple myeloma and other select B-Cell lymphomas.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Fast Track Designation furthers our efforts to expeditiously develop CLR 131 as a new, innovative therapy for patients with relapse/refractory multiple myeloma", said James Caruso, president and CEO of Cellectar. "Patients with third line or later relapsed/refractory multiple myeloma have a poor prognosis and low rates of survival as a result of limited effective treatment options. Based on data in the initial patient cohort from our ongoing CLOVER-1 trial where patients showed a 30% response rate after receiving a single 25.0 mCi/m2 dose as a seventh line of therapy on average, we are optimistic that CLR 131 has the potential to provide a meaningful treatment option for these patients."

Fast Track Designation

Fast Track Designation is granted to drugs being developed for the treatment of serious or life-threatening diseases or conditions where there is an unmet medical need. The purpose of the Fast Track Designation provision is to help facilitate development and expedite the review of drugs to treat serious and life-threatening conditions.

Sponsors of drugs that receive Fast Track Designation have the opportunity for more frequent interactions with the FDA review team throughout the development program. These interactions may include meetings to discuss study design, data required to support approval, or other aspects of the clinical program. Additionally, products that have been granted Fast Track Designation may be eligible for priority review of a New Drug Application (NDA) and the FDA may consider reviewing portions of an NDA before the sponsor submits the complete application (Rolling Review).

About the Phase 2 CLOVER-1 Trial

CLOVER-1 is a Phase 2 study of CLR 131 being conducted in approximately 10 leading cancer centers in the United States in patients with relapsed or refractory B-cell hematologic cancers. The hematologic cancers being studied in the trial include multiple myeloma (MM), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL).

The study’s primary endpoint is clinical benefit response (CBR), with additional endpoints of overall response rate (ORR), progression free survival (PFS), median overall survival (OS) and other markers of efficacy following a fractionated dose of 15.625 mCi/m2 dose of CLR 131 administered on day 1 and day 8, with the option for a second dose cycle approximately 75-180 days later.

In addition to receiving the two fractionated doses of CLR 131, MM patients will receive 40 mg oral dexamethasone weekly for up to 12 weeks. Efficacy responses will be determined by the latest International Multiple Myeloma Working Group criteria. Efficacy for all lymphoma patients will be determined according to Lugano criteria. Cellectar was awarded approximately $2 million in non-dilutive grant funding from the National Cancer Institute to help fund the trial. More information about the trial, including eligibility requirements, can be found at www.clinicaltrials.gov, reference NCT02952508.

About CLR 131

CLR 131 is a small-molecule, cancer-targeting radiotherapeutic PDC designed to deliver cytotoxic radiation directly and selectively to cancer cells and cancer stem cells. CLR 131 is the company’s lead therapeutic PDC product candidate and is currently being evaluated in both Phase 2 and Phase 1 clinical studies. In December 2014, the FDA granted orphan drug designation for CLR 131 for the treatment of multiple myeloma. In 2018, the FDA granted orphan drug and rare pediatric disease designations for CLR 131 for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. In addition to the ongoing Phase 1 dose-escalation study and the Phase 2 CLOVER-1 trial, the company recently initiated a Phase 1 open-label, dose-escalating study in pediatric solid tumors and lymphoma to evaluate the safety and tolerability of a single intravenous administration of CLR 131 in up to 30 children and adolescents with cancers including neuroblastoma, sarcomas, lymphomas (including Hodgkin’s lymphoma) and malignant brain tumors.

On May 13, 2019 GRAIL, Inc., a healthcare company whose mission is to detect cancer early, when it can be cured, reported that its multi-cancer test has been granted Breakthrough Device designation from the U.S. Food and Drug Administration (FDA) (Press release, Grail, MAY 13, 2019, View Source [SID1234536233]). The investigational blood test is in development for the early detection of multiple cancer types in individuals aged 50 or older. The FDA grants Breakthrough designation to devices that have the potential to provide for more effective diagnosis of life-threatening diseases such as cancer. The goal of the FDA’s Breakthrough Devices Program is to provide patients and healthcare providers with timely access to medical devices granted the designation by speeding up their development, assessment, and review.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We’re excited the FDA recognizes the potential of our multi-cancer early detection blood test. There are no effective early detection tests for the majority of cancer types, and many deadly cancers are often detected too late. We hope our test may offer a chance to address these challenges," said Jennifer Cook, Chief Executive Officer. "We have made significant progress developing our multi-cancer test and look forward to sharing new data at ASCO (Free ASCO Whitepaper) and other medical conferences this year."

GRAIL previously reported data from the first pre-planned sub-study of its Circulating Cell-free Genome Atlas (CCGA) study, which showed that its three prototype next-generation sequencing (NGS) blood tests were able to detect multiple deadly cancer types from a single blood draw, with a low rate of false positive results (high specificity).1 The company has since selected methylation as its preferred approach and has developed a methylation sequencing blood test that preferentially targets the most informative regions of the genome to both detect the presence of multiple types of cancer and identify the tissue of origin (the part of the body where the cancer originated). The blood test is currently being evaluated in the second pre-planned sub-study of CCGA.

New results from CCGA will be presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, including data on the ability of the company’s methylation technology to identify the tissue of origin when cancer is present. An analysis of survival of participants whose cancer was detected by the methylation technology, compared with those whose cancer was not detected by the technology, will also be presented.

About GRAIL’s Clinical Program

GRAIL is conducting what the company believes to be one of the largest clinical research programs ever pursued in genomic medicine. The program consists of three large-scale studies designed to enroll approximately 165,000 participants to create an atlas of genomic cancer signals in the blood, and to develop and evaluate GRAIL’s blood test for the early detection of multiple cancer types. Approximately 115,000 participants have been enrolled to date.

The CCGA study is a prospective, observational, longitudinal study that has completed enrollment of approximately 15,000 people with and without cancer across 142 sites in the United States and Canada. GRAIL is conducting three pre-planned sub-studies within CCGA to discover, train, and validate its multi-cancer early detection test.

The STRIVE study is a prospective, observational, longitudinal cohort study that has completed enrollment of approximately 100,000 women at the time of their screening mammogram across 37 sites in the United States. STRIVE is designed for clinical validation of GRAIL’s multi-cancer test in an intended use population. GRAIL anticipates reporting data from STRIVE in 2020.

The SUMMIT study is a prospective, observational, longitudinal cohort study that is enrolling participants in London in the United Kingdom. The study is designed to enroll approximately 50,000 men and women who do not have a cancer diagnosis at the time of enrollment. Approximately half of the participants will be people at high risk of lung and other cancers due to a significant smoking history, and the other half will be people who are not at high risk for cancer based on smoking history. SUMMIT is designed for clinical validation of GRAIL’s multi-cancer test in a second intended use population and to evaluate clinical utility of the test in a high-risk population.

About GRAIL’s Methylation Technology

GRAIL is developing an NGS blood test for the early detection of multiple deadly cancer types. GRAIL’s methylation technology preferentially targets the most informative regions of the genome and uses machine-learning algorithms to both detect the presence of cancer and identify the tumor’s tissue of origin when cancer is present.

DNA methylation is a natural process used by cells to regulate gene expression. It is a chemical modification to DNA and a well-studied epigenomic feature of the genome. In cancer, abnormal methylation patterns and the resulting changes in gene expression can contribute to tumor growth. For example, hypermethylation can cause tumor-suppressor genes to be inactivated.