On July 13, 2021 AVM Biotechnology, a clinical-stage company, reported that FDA permission to modify its ongoing clinical study, AVM0703-001, entitled "The WWRD Study: AVM0703 for Treatment of Leukemia or Lymphoma" (Press release, AVM Biotechnology, JUL 13, 2021, View Source [SID1234584822]). The initial protocol, a 3 x 3-based design, called for dose escalation of 3 mg/kg for each of the six cohorts, ranging from 6 mg/kg to 21 mg/kg, with a minimum of three patients per cohort as part of an adaptive-design/expansion cohort trial.

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The approved protocol modification involves the elimination of three of the cohorts and reduction of the interval between cohorts. Eliminating the 9, 12 and 15 mg/kg dose requirements and moving directly to the anticipated effective clinical dose of 18 mg/kg is important for this study. Preclinical research and compassionate use data indicate 18-21 mg/kg will be the target effective dose for the expansion phase of the study. Bypassing the intermediate dose levels should accelerate completion of the dose-escalation part of the study, enabling the efficacy portion to commence immediately thereafter, much sooner than planned.

"We are pleased that the FDA agreed with our proposal, which leveraged the safety data amassed from the ongoing study and Expanded Access (Compassionate Use) patient data obtained to date," remarked Janet R Rea, MSPH, Chief Regulatory Officer. "This accelerates our clinical development program and propels it toward an earlier NDA submission."

Clinical experience has shown the drug to be well tolerated with mild and self-limiting side effects. Patients have reported feeling "great." The emerging safety profile is promising, to treat these seriously ill patients.

A single dose of AVM0703 triggers the rapid activation and mobilization of novel gamma delta positive Natural Killer T (NKT) cells. NKT cells exhibit properties of both innate and adaptive immunity. AVM-NKT cells home to abnormal cells including cancer and autoreactive lymphocytes sparing platelets, red blood cells and stem cells. These unique AVM-NKT cells could play a significant role in addressing several serious conditions, including various types of cancer and autoimmune diseases such as type 1 diabetes. Preclinical data also indicate AVM0703 can be synergistic with chemotherapy, allowing total cycles of chemotherapy to be reduced while maintaining patient response, thus significantly impacting patient quality of life, treatment compliance, and secondary complications from cancer treatment.

"AVM has developed an entirely new drug that demonstrates a novel mechanism of action related to tissue-bound gamma delta NKT cells. We believe this drug will have great benefit to patients in a wide variety of disease settings," stated AVM Chief Business Officer, Joe Luminiello.

AVM Biotechnology is a clinical-stage company advancing AVM0703 in Non-Hodgkin’s Lymphoma/Leukemia as an initial indication as well as autoimmune diseases and other indications. While planning for a direct commercial launch of AVM0703, the company is also developing the AVM-NKT as an ‘off-the-shelf’ cell therapy product with broad applications. Strategic partnerships are being explored.

AVM Biotechnology’s mission is to develop and deliver treatments that save lives and improve outcomes by unlocking the untapped potential of the body’s own immune system.

On July 12, 2021 Patrys reported new data confirming its full-sized IgG deoxymab antibody, PAT-DX3, is able to cross the blood-brain barrier (BBB) in animal models of primary brain cancer (Press release, Patrys, JUL 12, 2021, View Source [SID1234584770]).

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This data follows recent studies showing the deoxymab antibody fragment, PAT-DX1, is able to cross the BBB in animal models of primary and secondary brain cancer.

Most antibodies are unable to cross cell membranes or the blood-brain barrier, limiting their use in treating cancers of the brain. However, Dr James Hansen at Yale School of Medicine has shown the potential of Patrys’ lead deoxymab, PAT-DX1, for tackling these difficult-to-reach-and-treat cancers.

The Company plans to conduct follow up studies to compare the effects of both PAT-DX3 and PAT-DX1 on tumour reduction and survival in brain cancer.

Patrys CEO and MD, Dr James Campbell said:

We are very excited by this new discovery that opens up a range of development and partnering opportunities for Patrys around PAT-DX3. As PAT-DX3 shares a common mechanism of action with PAT-DX1, it is expected that it will also localise to both primary and secondary tumours in the brain and selectively kill cancer cells by blocking their DNA Damage Repair (DDR) systems.

On July 12, 2021 OPKO Health, Inc. (NASDAQ: OPK) reported it has entered into an exclusive worldwide agreement with privately held CAMP4 Therapeutics Corporation (CAMP4) for the development, manufacture and commercialization of therapeutics utilizing the AntagoNAT technology, an oligonucleotide platform developed under OPKO CURNA (Press release, Opko Health, JUL 12, 2021, View Source [SID1234584787]). AntagoNATs are oligonucleotide compounds that target non-coding natural antisense transcripts leading to an upregulation of a desired functional protein. CAMP4 has prioritized OPKO’s lead AntagoNAT compound to progress into clinical trials for the treatment of Dravet syndrome.

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Under the terms of the agreement, OPKO will receive an upfront payment and shares of CAMP4. In addition, OPKO will be eligible to receive up to $93.5 million and additional shares upon the achievement of certain development and sales milestones for products developed from this technology and associated intellectual property. CAMP4 will also pay OPKO double-digit royalties on product sales.

"We are delighted to enter into this licensing agreement to accelerate the development and commercialization of potential disease-modifying therapeutics. With a clear focus on therapeutics that restore healthy gene expression, CAMP4 has the expertise to advance our Dravet syndrome compound through the necessary patient trials. This agreement validates our technology and allows OPKO to focus resources on other areas of our business. We continue to seek license opportunities to monetize and leverage our early-stage assets," said Phillip Frost, M.D., Chairman and Chief Executive Officer of OPKO.

According to the Epilepsy Foundation, Dravet syndrome is a rare, drug-resistant epilepsy that begins in the first year of life in an otherwise healthy infant. It is estimated that 1-in-20,000 to 1-in-40,000 individuals have Dravet syndrome. Most cases are due to SCN1A gene mutations and most children develop varying degrees of neurodevelopmental disability.

CAMP4 is pioneering a novel approach to programmable therapeutics that combines a deep understanding of regulatory RNA and gene expression with a complementary and customizable oligonucleotide modality. The company’s RNA Actuating Platform’s proprietary insights enable drug discovery and development that aims to harness the power of RNA to upregulate the expression of genes and unlock the potential to create treatments for hundreds of diseases affecting millions of patients.

On July 12, 2021 Caribou Biosciences, Inc., a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported that the first patient has been dosed in its open-label, multicenter ANTLER phase 1 clinical trial (NCT04637763) to evaluate the company’s lead product candidate, CB-010, in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) (Press release, Caribou Biosciences, JUL 12, 2021, View Source [SID1234584788]). CB-010 is an allogeneic anti-CD19 CAR-T cell therapy derived from healthy donor T cells that have been engineered using Caribou’s chRDNA technology to reduce the risk of graft versus host disease (GvHD) and knock out PD-1 to boost the persistence of CAR-T cell antitumor activity.

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"Advancing our first allogeneic CAR-T cell therapy into the clinic represents a major milestone for Caribou," said Rachel Haurwitz, Ph.D., Caribou’s president and chief executive officer. "Using our proprietary chRDNA CRISPR technology, we have developed a pipeline of off-the-shelf CAR-T and CAR-NK cell therapies with the potential to serve a greater number of patients than autologous approaches. We believe that improving cell persistence is the key to unlocking the full potential of these therapies. Using our technologies, we edit the genome of healthy donor-derived T cells to enable highly specific and efficient insertion or deletion of genes at multiple sites. This allows us to create sophisticated allogeneic cell therapies with enhanced characteristics to potentially improve their effectiveness and durability of antitumor activity compared to other allogeneic cell therapies. With CB-010, we are evaluating the potential persistence-enhancing effects of removing the PD-1 protein from the surface of these CD19-targeted CAR-T cells."

Cherry Thomas, M.D., senior vice president of clinical development, added, "We are thrilled to advance CB-010 in the clinic and believe it potentially represents a promising, differentiated therapy for patients. Initially, we will evaluate escalating doses of CB-010 in relapsed or refractory B cell non-Hodgkin lymphoma patients with the goals of assessing safety and tolerability and to establish a dose level for the expansion phase of the study. We look forward to having initial clinical data from this clinical trial in 2022."

About CB-010

CB-010 is an allogeneic anti-CD19 CAR-T cell therapy derived from healthy donor T cells. The cells are engineered using Caribou’s chRDNA CRISPR technology to integrate a CD19-CAR site-specifically into the T cell genome at the site of the TRAC gene locus, thus eliminating expression of the T cell receptor to reduce the risk of GvHD. The cells are modified further using chRDNA to knock out the gene encoding PD-1, thus preventing the expression of the PD-1 protein on the CAR-T cell surface. Elimination of PD-1 expression is designed to boost the persistence of CAR-T cell antitumor activity by reducing CB-010 exhaustion and thereby potentially providing a better therapeutic index compared to other allogeneic CAR-T cells. An additional step in the manufacturing process for CB-010 is designed to remove residual T cells expressing a T cell receptor, further reducing the risk of GvHD.

About the Phase 1, Dose Escalation Study of CB-010 (ANTLER Study, NCT04637763)

The ANTLER study is an open-label, multicenter phase 1 clinical trial designed to evaluate CB-010 in adults with r/r B-NHL. In the dose-escalation part of the study, adults who have failed at least two lines of chemo and/or immunotherapy will receive CB-010 following lymphodepletion. In a standard 3+3 dose escalation design, increasing doses of CB-010 will be evaluated to determine safety and tolerability and to establish a dose level for the expansion part of the study. The primary objective of the dose escalation is to evaluate the safety and tolerability of CB-010 and the primary objective of the expansion part of the study is to evaluate the efficacy of CB-010 in a defined population. Patients who have received a prior CD19-targeted therapy will be excluded from the study.

About Caribou’s Novel Next-Generation CRISPR Platform

CRISPR genome editing uses easily designed, modular biological tools to make DNA changes in living cells. There are two basic components of Type II CRISPR systems: the nuclease protein that cuts DNA and the RNA molecule(s) that guide the nuclease to generate a site-specific, double-stranded break, leading to an edit at the targeted genomic site. CRISPR systems occasionally edit unintended genomic sites, known as off-target editing, which may lead to harmful effects on cellular function and phenotype. In response to this challenge, Caribou has developed chRDNAs (pronounced "chardonnays"), RNA-DNA hybrid guides that direct substantially more precise genome editing compared to all-RNA guides. Caribou is deploying the power of the chRDNA technology to carry out high efficiency multiple edits, including multiplex gene insertions, to develop CRISPR-edited therapies.

On July 12, 2021 Tempus, a leader in artificial intelligence and precision medicine, reported results from validation studies demonstrating the reliable analytical performance of the Tempus|xF liquid biopsy (Press release, Tempus, JUL 12, 2021, View Source [SID1234584789]). When validated against methods such as ddPCR, the Roche AVENIO kit, and the Tempus|xT solid tumor assay, xF demonstrated high sensitivity and specificity for calling SNVs, indels, CNVs, and gene rearrangements, making the liquid biopsy next-generation sequencing assay a preferred sequencing option should tumor tissue not be available.

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xF is Tempus’ non-invasive, 105-gene liquid biopsy panel focused on oncogenic and resistance mutations in cell-free DNA. Designed to provide clinical decision support for solid tumors, xF is an alternative to tissue-based biopsies in identifying biomarkers, detecting resistant mutations, monitoring response to treatment or disease progression, and spotting early recurrence in real time. npj Precision Oncology published xF’s analytical validation, highlighting the assay’s high sensitivity and specificity for detecting single-nucleotide variants, insertions/deletions, copy number variants, and gene rearrangements. The validation results show high accuracy in detecting clinically-actionable targets compared to orthogonal testing methods.

"This study underscores the clinical value of liquid biopsies, a non-invasive sequencing option and another powerful tool for oncologists to determine clinically-actionable alterations necessary for highly-effective and personalized treatment options," said Dr. Kimberly Blackwell, Chief Medical Officer at Tempus. "At Tempus, we have also found that xF is especially beneficial when used in combination with standard tissue sequencing for patients with advanced cancer, and therefore it is important to offer oncologists both a liquid biopsy and solid tumor assay on a single platform."

xF is part of Tempus’ library of assays conducted in its CLIA-certified and CAP-accredited laboratory, which also includes xE, an assay that analyzes the whole exome and xT, an assay that analyzes 648 genes in solid tumor and hematologic malignancies.