On August 3, 2020 vTv Therapeutics Inc. (Nasdaq:VTVT) reported financial results for the second quarter ended June 30, 2020, and provided an update on the progress of its clinical programs (Press release, vTv Therapeutics, AUG 3, 2020, View Source [SID1234562742]).

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"Building on the successful phase 2 study completed earlier this year with TTP399, we have been highly focused on advancing this promising candidate as an adjunct to insulin for type 1 diabetes into the next stage of clinical development," said Steve Holcombe, president and CEO. "To this end, we have been engaging with the FDA to determine the development path for TTP399 and are in the planning stages for our first pivotal study, which we anticipate commencing by the end of 2020. We have also continued to enroll patients in our phase 2 study of azeliragon for the treatment of Alzheimer’s disease in patients with type 2 diabetes, despite the clinical challenges posed by COVID-19."

Recent Achievements and Outlook

Type 1 Diabetes

FDA Engagement and Pivotal Study Planning. Following a Type C Meeting request, vTv received written feedback from the FDA in June regarding the design of the Company’s proposed pivotal studies. vTv expects to commence the next study for TTP399 by the end of 2020 with a six-month treatment period and a six-month open label extension. A second study with a 6-month treatment period would be initiated within 12 months after initiation of the first trial.

Two Presentations at ADA of SimpliciT-1 Study Results. Dr. John Buse, University of North Carolina at Chapel Hill, and Dr. Carmen Valcarce, chief scientific officer, made separate presentations at the American Diabetes Association’s 80th Scientific Sessions on the results of the Simplici-T1 Study in which TTP399 improved HbA1c in patients with type 1 diabetes, while reducing insulin dose and lowering the incidence of hypoglycemia and diabetic ketoacidosis.

Dementia with Diabetes

Enrollment continues for Phase 2 Elevage Study of azeliragon. vTv continues to enroll patients in the Elevage Study to evaluate the efficacy and safety of azeliragon in patients with probable mild Alzheimer’s disease (AD) and type 2 diabetes. Recruitment for the study will conclude by September 30, 2020 with a target of approximately 50 patients enrolled. The Company expects to report topline results from this study in the second quarter of 2021.

Additional Clinical Data from STEADFAST Presented at AAIC. Dr. Aaron Burstein, SVP clinical development, presented additional clinical data at the Alzheimer’s Association International Conference of the impact of azeliragon on the individual

components of CDR-sb and ADAS-cog, the two primary instruments used to evaluate Alzheimer’s disease.

Financing Activities

During the second quarter, vTv entered into agreements in order to provide additional financial flexibility and availability of additional capital to fund its near-term operations.

Amendment to the Loan Agreement. On July 29, 2020, vTv entered into the Third Amendment to the Company’s existing Loan Agreement to allow monthly, interest-only payments on the outstanding principal balance for two additional months beginning July 1, 2020 and to extend the maturity date of the first tranche from August 1 to September 1, 2020. The Third Amendment also eliminates the requirement for the Company to maintain a minimum cash balance.

ATM Sales. Under the Controlled Equity OfferingSM Sales Agreement with Cantor Fitzgerald, vTv sold shares of its Class A common stock having an aggregate offering price of $7.6 million as of the end of the second quarter.

Second Quarter 2020 Financial Results

Cash Position: The Company’s cash position as of June 30, 2020, was $6.4 million compared to $0.4 million as of March 31, 2020.

Revenue: Revenues were insignificant for both the first and second quarter of 2020.

R&D Expenses: Research and development expenses were $2.5 million and $4.2 million for the three months ended June 30, 2020 and March 31, 2020, respectively. This decrease of $1.7 million was driven primarily by a decrease of $0.5 million related to the development of TTP399, as the Simplici-T1 Study was completed in early 2020. Further, costs related to the development of azeliragon decreased approximately $0.8 million related to lower costs incurred for the Elevage Study due to a slowdown in enrollment caused, in part, by COVID-19.

G&A Expenses: General and administrative expenses were $1.7 million for the second quarter of 2020 and $2.5 million for the first quarter, respectively. The decrease of $0.8 million was driven by lower professional fees, an adjustment made to the Company’s asset retirement obligation recorded in connection with a leased facility, and overall expense curtailment.

Net Loss Before Non-Controlling Interest: Net loss before non-controlling interest was $5.0 million for the second quarter of 2020 compared to $7.2 million for the first quarter of 2020.

Net Loss Per Share: GAAP net loss per share was $0.07 and $0.11 for the three months ended June 30, 2020 and March 31, 2020, respectively, based on weighted-average shares of 45.7 million and 43.5 million for the three-month periods ended June 30, 2020 and March 31, 2020, respectively. Non-GAAP net loss per fully exchanged share was $0.08 and $0.11 for the three months ended June 30, 2020 and March 31, 2020, respectively, based on non-GAAP fully exchanged weighted-average shares of 68.8 million

On August 3, 2020 Pacific Biosciences of California, Inc. (Nasdaq:PACB), a leading provider of high-quality sequencing of genomes, transcriptomes and epigenomes, and Asuragen, a molecular diagnostics company delivering easy-to-use products for complex testing in genetics and oncology, reported their clinical research collaboration aimed at developing molecular assays based on PacBio’s Single Molecule, Real-Time (SMRT) Sequencing technology (Press release, Pacific Biosciences, AUG 3, 2020, View Source [SID1234562722]). The initial focus of the collaboration will be on research in support of assay development for the carrier screening market.

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Several of the most common carrier genes for autosomal recessive and X-linked conditions are either technically challenging or inaccessible to amplify and sequence, leading to incomplete coverage and convoluted workflows spread over multiple platforms. Through this collaboration, Asuragen scientists will develop assays that combine the company’s AmplideX PCR technology for enriching hard-to-amplify sequences with PacBio SMRT Sequencing, a highly accurate long-read sequencing platform with a unique ability to represent all regions of the genome and to detect any kind of structural or other variation.

"Innovative amplification and sequencing technologies have each been instrumental in discovering and characterizing challenging disease-causing structural variants, such as indels, copy number changes, and repeat expansions," said Gary J. Latham, PhD, Senior Vice President of Research and Development at Asuragen. "We are excited to work with PacBio to combine the best of both technologies to build assays that can uniformly resolve simple and complex forms of genetic variation for research and clinical applications."

Scientists at Asuragen will develop assays for PacBio’s Sequel Systems using Asuragen’s AmplideX PCR technology. AmplideX products are designed to solve testing needs in inherited genetic disorders through easy-to-run assays and optimized workflows that deliver best-in-class performance. Assays will make use of PacBio’s HiFi long reads, an approach incorporating multiple passes of the same molecule to create a highly accurate consensus sequence.

"We are honored to partner with Asuragen, a leader in molecular diagnostics, to apply the unique value of SMRT Sequencing for clinical research," said Jonas Korlach, PhD, Chief Scientific Officer of Pacific Biosciences. "Scientists have shown that PacBio’s long-read sequencing systems offer a high-resolution view of the human genome that is simply not possible with any other sequencing technology. We look forward to working with Asuragen to design assays capable of interrogating challenging genomic regions and identifying the full breadth of natural human genetic variation."

On August 3, 2020 Simcere Pharmaceutical Group Co., Ltd. (hereinafter referred to as "Simcere") and tumor clinical stage company G1 Therapeutics Company ( Nasdaq: GTHX ), reported the signing of an exclusive license to introduce Trilaciclib ‘s development and commercialization rights for all indications in Greater China (Mainland China, Hong Kong, Macau and Taiwan) (Press release, Jiangsu Simcere Pharmaceutical Company, AUG 3, 2020, View Source [SID1234562741]). Trilaciclib is the world’s first innovative drug discovered and developed by G1 to improve the prognosis of cancer patients after chemotherapy.

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" Trilaciclib may become the first prophylactically administered bone marrow protective therapy, which can effectively improve the prognosis of patients undergoing chemotherapy. We are very pleased to cooperate with Simcere , a Chinese company with leading innovative drug development and commercialization capabilities. , To promote this innovative therapy in China," said G1 CEO and MD Dr. Mark Velleca . "Sincere Pharmaceuticals has extensive experience in drug clinical trials and drug registration in China, and has a nationwide professional team that supports product academic promotion and market access. These advantages make them an important strategic partner of G1 to realize our The vision of bringing Trilaciclib to patients around the world."

According to the terms of the agreement, G1 will receive a down payment of US$ 14 million, and will receive development and commercialization milestone payments of up to US$ 156 million. Simultaneously, Simcere Pharmaceuticals will pay G1 low double-digit sales commission based on Trilaciclib ‘s annual net sales in Greater China . Simcere Pharmaceuticals will have the exclusive rights to develop and commercialize Trilaciclib for all indications in Greater China, and will participate in Trilaciclib ‘s global clinical trials. G1 reserves the right to develop and commercialize Trilaciclib in all regions outside the Greater China region. Both parties will be responsible for all development and commercialization costs in their respective regions.

Dr. Wang Pin, Chief Scientific Officer of Simcere Pharmaceuticals, said: "Currently, chemotherapy is the cornerstone therapy for cancer patients. A large number of patients in China are suffering from bone marrow suppression caused by chemotherapy. We are very pleased to have a deep cooperation with G1 Therapeutics in China. Developed and commercialized Trilaciclib , the world’s first product of its kind to protect bone marrow . We look forward to further expanding its clinical value based on Trilaciclib’s unique mechanism. We hope that through the joint efforts of both parties, Trilaciclib can benefit more cancer patients around the world as soon as possible."

Lung cancer is the most common cancer in the world, and small cell lung cancer accounts for about 15% of all lung cancer cases . According to statistics from the International Agency for Research on Cancer ( IARC ), a specialized cancer agency of the World Health Organization ( WHO ) , nearly 750,000 new lung cancer cases were reported in China in 2018 .

About Trilaciclib

Trilaciclib is the world’s first innovative product of its kind designed to improve the prognosis of cancer patients with chemotherapy. Trilaciclib is given before chemotherapy in patients with small cell lung cancer ( SCLC ). Based on the bone marrow protection data of three randomized, double-blind, placebo-controlled clinical trials in the United States, it has obtained FDA breakthrough therapy designation. In a randomized trial of patients with metastatic triple-negative breast cancer, compared with chemotherapy alone, trilaciclib when used in combination with chemotherapy significantly improved the overall survival of the patient. In 2020 Nian 6 Yue, G1 in the United States submitted a new drug application ( NDA ), is used to protect the bone marrow of patients with small cell lung cancer, and as I-Spy2 part of a pilot study began neoadjuvant chemotherapy. G1 expects to initiate a Phase III registered clinical trial for colorectal cancer in the United States in the fourth quarter of 2020 .

On August 3, 2020 Karius, the world leader in liquid biopsy for infectious diseases, reported active enrollment in a multicenter, prospective study that will evaluate the diagnostic value of the Karius Test for pneumonia in immunocompromised adult patients including those with hematological cancers (Press release, Karius, AUG 3, 2020, View Source [SID1234562734]). The Karius Test is a non-invasive blood test based on next-generation sequencing of microbial cell-free DNA that can rapidly detect over 1,000 bacteria, DNA viruses, fungi, and parasites. The test is currently being used by over 100 hospitals nationwide.

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The "Pneumonia in the ImmunoCompromised – Use of the Karius Test for the Detection of Undiagnosed Pathogens" (PICKUP) study will compare the diagnostic yield of the Karius Test to standard testing methods used to diagnose infectious causes of pneumonia in immunocompromised patients including those with hematological cancers. Patients with suppressed immune systems are especially vulnerable to life-threatening pneumonias due to their decreased ability to fight infections. Standard methods to diagnose pneumonia can be invasive, time-consuming (requiring weeks to months for a result), and inconclusive, often failing to identify the pathogen causing the infection. The PICKUP study will investigate the additive diagnostic value of the Karius Test in the diagnosis of pneumonia in these patients and its impact on clinical decision-making in this specific population. In addition, the Karius Test will be used to serially monitor pathogen levels during treatment to examine the association between microbial load and pneumonia progression.

"The ability to diagnose invasive life-threatening infections in immunocompromised patients has been one of the most challenging areas in clinical infectious disease practice," said Karius CEO, Mickey Kertesz. "We are enthusiastic to be collaborating with a number of leading cancer centers for this study and anticipate that the Karius Test will demonstrate a higher diagnostic yield than traditional invasive testing methods."

"Often in pneumonia, the causative pathogen is unknown or can be challenging to diagnose despite extensive diagnostic testing," said Dr. Stephen Bergin, Assistant Professor of Pulmonary and Critical Care Medicine at Duke University Health System and lead investigator for the PICKUP study. "Accurate and timely pathogen identification is particularly critical for immunocompromised patients who are susceptible to life-threatening infections from a much broader array of pathogens. We look forward to exploring the potential value of a non-invasive tool capable of rapidly diagnosing respiratory infections in this vulnerable population."

Previous studies have demonstrated the ability of the Karius Test to overcome many of these limitations to diagnose the cause of pneumonia and enable targeted treatment. The study will include approximately 200 patients from up to 10 centers in the United States.

On August 3, 2020 Natera, Inc. (NASDAQ: NTRA), a pioneer and global leader in cell-free DNA testing, reported the publication of a manuscript in Nature Cancer1 that validates the ability of its Signatera personalized circulating tumor DNA (ctDNA) technology to evaluate tumor response to immunotherapy in 25 different types of solid cancer (Press release, Natera, AUG 3, 2020, View Source [SID1234562731]). The full study can be found here.

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"Although immune checkpoint inhibitors are an effective tool for treating many types of cancer, the decision to treat beyond radiological progression can sometimes be challenging due to potential pseudo-progression," explained Lillian Siu, MD, FRCPC, BMO Chair in Precision Cancer Genomics at the Princess Margaret Cancer Centre and lead investigator of the study. "We are delighted to have partnered with Natera on this landmark study, which shows that ctDNA-based surveillance using the Signatera test, in conjunction with imaging, can be used to identify true disease progression and thus help patients receive appropriate immunotherapy treatment."

Pseudo-progression is a phenomenon whereby the tumor appears larger on an initial scan during treatment before shrinking on subsequent scans, and it has been reported in up to 1 in 10 patients treated with immunotherapy.2,3 The ability to distinguish true progression from pseudo-progression, earlier in the course of treatment, has emerged as a significant unmet clinical need.

The prospective phase II INSPIRE study, led by the Princess Margaret Cancer Centre in Toronto, followed patients with advanced solid tumors being treated with the immunotherapy drug, pembrolizumab. Whole exome sequencing was performed using tumor and matched normal DNA, and then bespoke ctDNA assays were designed using Signatera technology. ctDNA assessments were made at baseline in 94 patients, and every three cycles during treatment in 73 patients where serial plasma samples were available.

In the published manuscript, the study’s authors concluded, "The findings from this prospective study suggest broad clinical utility for ctDNA-based surveillance in patients treated with immune checkpoint blockade."

Key findings from the study include:

Signatera technology detected ctDNA before treatment in 98% of cases (92/94), emphasizing its validity as a universal biomarker across tumor types.
ctDNA increase after just 6 weeks of treatment, together with increasing tumor volume on imaging, was identified in 42% of patients (30/73) and predicted treatment non-response with 100% accuracy. These patients received on average 6 extra weeks of treatment that potentially could have been avoided.
ctDNA clearance at any time point during treatment was achieved by 16% of patients (12/73) and was associated with 100% overall survival with a median of 25.4 months of followup beyond first clearance.
All findings were independent of tumor mutational burden (TMB) and PD-L1 status.
"With over 200,000 patients per year being treated with immunotherapy,4 we see a significant opportunity for serial use of Signatera to help physicians determine treatment response earlier," said Solomon Moshkevich, General Manager of Natera’s oncology business. "We think this novel application could be as significant as Signatera’s use case in early-stage colorectal cancer."

We thank Merck for contributing the drug for this clinical trial.

About Signatera
Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for clinical and research use, and, in 2019, it was granted Breakthrough Device Designation by the U.S. Food and Drug Administration (FDA). The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. This maximizes accuracy for detecting the presence or absence of residual disease in a blood sample, even at levels down to a single tumor molecule in a tube of blood.
Unlike a standard liquid biopsy, Signatera is not intended to match patients with any particular therapy. Rather, it is intended to detect and quantify how much cancer is left in the body, to detect recurrence earlier, and to help optimize treatment decisions. Signatera test performance has been clinically validated in multiple cancer types including colorectal, non-small cell lung, breast, and bladder cancers. Medicare has proposed insurance coverage for the use of Signatera in patients with Stage II or III colorectal cancer, and it is expected to finalize that coverage decision in 2020. Signatera has been developed and its performance characteristics determined by the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). Although FDA is exercising enforcement discretion of premarket review and other FDA legal requirements for laboratory-developed tests in the US, certification of the laboratory is required under CLIA to ensure the quality and validity of the tests.