On June 22, 2021 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it obtained approval from the Ministry of Health, Labour and Welfare (MHLW) on June 21, 2021, for FoundationOne CDx Cancer Genomic Profile to be used as a companion diagnostic (CDx) for both a human anti-human PD-1 monoclonal antibody, Opdivo [generic name: nivolumab (genetical recombination)] and a humanized anti-human PD-1 monoclonal antibody, Keytruda [generic name: pembrolizumab (genetical recombination)] for the treatment of patients with microsatellite instability high (MSI-High) tumors (Press release, Chugai, JUN 22, 2021, View Source [SID1234584213]).

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"High microsatellite instability has been identified in tumors in various organs, and immune-checkpoint inhibitors can be a therapeutic option. FoundationOne CDx Cancer Genomic Profile is characterized by the ability to comprehensively capture information on individual gene alterations, as well as the ability to detect microsatellite instability," said Dr. Osamu Okuda, Chugai’s President and CEO. "Through testing with FoundationOne CDx Cancer Genomic Profile, we will contribute to ensuring as many patients as possible to have access to optimal treatments."

As a companion diagnostic, FoundationOne CDx Cancer Genomic Profile will be used to identify patients with MSI-High unresectable advanced or recurrent colorectal cancer that have progressed following chemotherapy who may benefit from nivolumab. It will also be used to identify patients with microsatellite instability (MSI-H) solid tumors that have advanced or relapsed after chemotherapy (limited to use when difficult to treat with standard of care), who may benefit from pembrolizumab.

As a leading company in the field of oncology, Chugai is committed to realizing advanced personalized oncology care and contributing to patients and healthcare professionals through improving access to comprehensive genomic profiling of cancers.

Approval information The underlined part has been newly added.

Intended uses or indications

The Product is used for comprehensive genomic profiling of tumor tissues in patients with solid cancers.
The Product is used for detecting gene mutations and other alterations to support the assessment of drug indications listed in the table below.
Alterations Cancer type Relevant drugs
Activated EGFR alterations Non-small cell lung cancer (NSCLC) afatinib dimaleate, erlotinib hydrochloride, gefitinib, osimertinib mesylate
EGFR exon 20 T790M alterations osimertinib mesylate
ALK fusion genes alectinib hydrochloride, crizotinib, ceritinib
ROS1 fusion genes entrectinib
MET exon 14 skipping alterations capmatinib hydrochloride hydrate
BRAF V600E and V600K alterations Malignant melanoma dabrafenib mesylate, trametinib dimethyl sulfoxide, vemurafenib
ERBB2 copy number alterations (HER2 gene amplification positive) Breast cancer trastuzumab (genetical recombination)
KRAS/NRAS wild-type Colorectal cancer cetuximab (genetical recombination), panitumumab (genetical recombination)
Microsatellite instability high nivolumab (genetical recombination)
Microsatellite instability high Solid tumors pembrolizumab (genetical recombination)
NTRK1/2/3 fusion gene entrectinib, larotrectinib sulfate
BRCA1/2 alterations Ovarian cancer olaparib
BRCA1/2 alterations Prostate cancer olaparib
FGFR2 fusion genes Biliary tract cancer pemigatinib
About FoundationOne CDx Cancer Genomic Profile
Developed by Foundation Medicine Inc., FoundationOne CDx Cancer Genomic Profile is a next-generation sequencing based in vitro diagnostic device for the detection of substitutions, insertion and deletion alterations, and copy number alterations in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens. The program is available as a companion diagnostic for multiple molecular-targeted drugs approved in Japan.

About Microsatellite instability high (MSI-High)
The genome contains several short strings of DNA (deoxyribonucleic acid) called microsatellites that are repeated many times. High-frequency microsatellite instability (MSI-High) is an abnormal number of microsatellite repeats1). Abnormal microsatellites do not lead to cancer, but tissues that show MSI-High are thought to be more likely to develop cancer. MSI-High has been found in patients with cancer of various organs, including endometrial, gastric, small intestine, colorectal, ovarian, renal pelvis/ureteral, prostate, and breast cancers2, 3). MSI-High is also a hallmark of people with Lynch syndrome who are born with genomic alterations that predispose them to developing cancer3).

Trademarks used or mentioned in this release are protected by laws.

[Reference]

Nojadeh, J.N. et al.: Microsatellite instability in colorectal cancer. EXCLI J. 17: 159-168, 2018.
Japan Society of Cancer Therapy/Japanese Society of Clinical Oncology: Guidelines for Transversal Genomic Practice in Organs in Adult and Pediatric Advanced Solid Tumors, Second Edition, October 2019
Colorectal Cancer Study Group: Hereditary Colorectal Cancer Guidelines 2020 Version

On June 22, 2021 Anavex Life Sciences Corp. ("Anavex" or the "Company") (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) disorders, reported that it has entered into a definitive purchase agreement with Deep Track Capital for the issuance and sale of an aggregate of 2,380,953 shares of its common stock at a purchase price of $21.00 per share of common stock a registered direct offering (Press release, Anavex Life Sciences, JUN 22, 2021, View Source [SID1234584212]). The registered direct offering is expected to close on or about June 24, 2021, subject to the satisfaction of customary closing conditions.

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H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The gross proceeds from the offering are expected to be approximately $50 million before deducting placement agent fees and other offering expenses. Anavex currently intends to use the net proceeds from the offering for advancing its pipeline and for working capital and general corporate purposes.

The shares of common stock described above are being offered pursuant to Anavex’s shelf registration statement on Form S-3 (File No. 333-232550) filed with the Securities and Exchange Commission (the "SEC") on July 3, 2019 and declared effective on July 15, 2019. Such shares of common stock may be offered only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and the accompanying prospectus relating to the shares of common stock being offered in the registered direct offering will be filed with the SEC. Electronic copies of the final prospectus supplement and the accompanying prospectus may be obtained, when available, on the SEC’s website at View Source or by contacting H.C. Wainwright & Co., LLC, 430 Park Avenue, 3rd Floor, New York, NY 10022, by e-mail: [email protected] or by telephone: (212) 856-5711.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of any of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such jurisdiction.

On June 22, 2021 Targovax ASA (OSE: TRVX), a clinical stage immune-oncology company developing immune activators to target hard-to-treat solid tumors, reported that its lead clinical candidate ONCOS-102 has received Fast Track designation in PD-1-refractory advanced melanoma from the US FDA (Press release, Targovax, JUN 22, 2021, View Source [SID1234584210]).

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The US FDA has granted Fast Track designation to ONCOS-102 based on the current pre-clinical and clinical data package, including mechanistic evidence showing an association between ONCOS-102-induced immune activation and tumor responses. Receiving this designation is an endorsement by the US FDA of the strength and importance of the ONCOS-102 data package in PD-1-refractory advanced melanoma. This Fast Track approval comes in addition to ONCOS-102´s existing Fast Track designation in malignant pleural mesothelioma.

The FDA Fast Track designation is awarded to therapies with potential to address unmet medical needs in serious medical conditions and allows for more frequent interactions with the FDA to expedite clinical development, as well as the regulatory review processes. Fast Track products have high likelihood of receiving Priority Review for a future Biologics License Application (BLA) and may be allowed to submit parts of the application for rolling review to shorten the approval timeline.

Dr. Ingunn Munch Lindvig, VP Regulatory Affairs of Targovax said: "Securing yet another Fast Track designation is a strong endorsement of the potential for ONCOS-102 to benefit a patient population with high unmet medical need. Fast Track simplifies and expedites the regulatory interactions and review process, and further supports the rationale for initiating a Phase 2 trial to target accelerated approval for ONCOS-102 in PD-1-refractory advanced melanoma".

On June 22, 2021 Race Oncology Limited ("Race") reported that it has executed an agreement with The Sheba Fund for Health Services and Research, Chaim Sheba Medical Center to commence a Phase 1b/2 trial in relapsed/refractory Acute Myeloid Leukaemia (R/R AML) (Press release, Race Oncology, JUN 22, 2021, View Source [SID1234584209]). This investigator-led trial will be supervised by Professor Arnon Nagler, who was the Principal Investigator on the Phase 2 investigator-initiated trial which reported an impressive 40% response rate as a single agent in R/R AML (ASX Announcement: 16 June 2020).

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This Phase 1b/2 trial will use Bisantrene in a novel three drug combination which in preclinical studies showed superior efficacy in AML cells (ASX Announcement: 10 May 2021). The trial has received human ethics approval and the first patient is expected to be treated in quarter 3 CY 2021.

The trial will run in parallel with a separate Australian Phase 2 trial in patients with extramedullary AML that is expected to begin treating patients in Q4 CY 2021 (ASX Announcement: 2 June 2021).

Both trials form key components of Race’s ‘3 Pillar’ strategy announced at the 2020 AGM (ASX Announcement: 30 November 2020).

Relapsed or Refractory Acute Myeloid Leukemia
Primary refractory or relapsed acute myeloid leukemia is associated with poor prognosis and remains a major therapeutic challenge. Primary refractory AML is defined by the absence of complete remission (CR), manifested by blast count of ≥5% in bone marrow after one or two cycles of intense induction chemotherapy.

Up to 30% of adults with newly diagnosed AML fail to achieve CR after two courses of intensive chemotherapy.

Even when CR is achieved through intense chemotherapy, approximately half of the younger and 80% of the older patients relapse. In both clinical situations, refractory and/or relapsed AML, active disease remains a major therapeutic challenge despite recent advances.

"Relapsed and refractory Acute Myeloid Leukaemia remains a significant challenge for patients and although there have been therapeutic advances in recent years, clinical outcomes are often suboptimal. This trial follows on from the Bisantrene monotherapy study sponsored by the Sheba Medical Centre, which reported promising results last year. In this new trial, we’re using a combination approach as identified by MD Anderson’s Professor Borje Andersson and published recently in the Journal of Clinical and Experimental Oncology. We hope to see that this combination approach will provide synergistic therapeutic benefit and enable patient dosing at lower levels than where either drug is used on its own."

Chaim Sheba Professor Arnon Nagler
Clinical Trial Design
An open-label, Phase 1b/2 study of intravenous FluCloXan ( Fludarabine, Clofarabine, Bisantrene dihydrochloride (Xan)) in cohorts of adult patients with R/R AML using a Simon’s 2-stage design: a Phase 1b lead-in dose escalation stage to establish the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of FluCloXan and a Phase 2 expansion stage to determine efficacy and confirm safety of the FluCloXan regimen at the RP2D in up to 17 subjects.

Phase 1b, Dose-Escalation (Lead-in Stage)
A two-cohort dose escalation schema using a 3 + 3 design will be employed.

Cohort 1 will enroll three subjects to receive the FluCloXan regimen for four consecutive days. If no dose limiting toxicities (DLTs) have occurred in the first three subjects by day 30 of their first cycle of treatment, then dose escalation to Cohort 2 will occur.

Phase 2, Expansion (Efficacy Stage)
Up to 17 subjects will be enrolled into a Phase 2 expansion efficacy cohort using a 2-stage Simon design. Initially, 9 subjects will be enrolled and treated with the recommended dose of FluCloXan regimen determined in Stage 1. If no subject responds according to the response criteria outlined in the European Leukemia Net (ELN) guidelines, in the first 9 subjects, the study will be terminated for futility. If at least one subject shows a response, 8 more subjects will be enrolled and treated. If three or more of subjects treated in Stage 2 respond, the null hypothesis can be rejected.

Efficacy assessments will be based on bone marrow examination at a minimum of two time points on Day 21 and on Day 30. A further bone marrow examination may be performed on Day 42 at the investigator’s discretion, based on the patient’s disease and performance status and/or on peripheral blood hematology results during the treatment course and between Day 21 to 42.

Treatment will be terminated upon any sign of progressive/recurrent disease and/or referral for starting pre-transplant conditioning therapy for (allogeneic) stem cell transplantation.

Subjects who do not progress or experience any dose limiting toxicities may receive a second course of treatment for the same duration as in their first cycle.

All subjects will be actively followed up every three months for a further 12 months following completion of Cycle 1 for disease free survival (DFS) and overall survival (OS).

While the focus of this trial is not aimed at targeting FTO driven cancers, the FTO expression status will be examined for each patient as part of an exploratory trial endpoint.

"We are delighted to be extending our successful collaboration with Prof Nagler and the team at Chaim Sheba using this novel combination approach for relapsed or refractory Acute Myeloid Leukaemia which remains an area of high unmet medical need. This study is an important part of our AML development plan for Bisantrene."

Race CMO Dr David Fuller
Indicative Costs and Timelines
The trial is expected to take 36 to 40 months to complete with full patient recruitment over approximately 18 months. Treatment of the first patient is targeted for Q3 CY 2021, subject to patient recruitment. Given its open-label status, Race expects that data will be reported at interim points throughout the trial.

Race will pay Chaim Sheba a maximum fee of USD $668,739 over the study’s life. Payments will be made to Chaim Sheba throughout the study upon reaching key milestones with the final trial cost dependent on the number of patients recruited and other operational variables.

"This study builds on our Pillar 3 ambitions to see Bisantrene’s historical safety and efficacy in AML demonstrated with superior drug combinations that may benefit patients who remain challenged by initial treatment failures. We hope to see the study confirming Bisantrene’s continued application as a differentiated chemotherapeutic with contemporary clinical relevance."

Race CEO & MD Phillip Lynch
Clinical Trial Summary
Study Title An Open-label, Phase 1b/2, Two-stage, Study of Xantrene (Bisantrene) in combination with Fludarabine and Clofarabine as Salvage Therapy for Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML)
Phase of Development Phase 1b/2
Active Ingredient Bisantrene dihydrochloride, Fludarabine, Clofarabine (FluCloXan)
Study Description Phase 1b/2 study of FluCloXan, in cohorts of adult patients with R/R AML using a 2-stage design: a Phase 1b lead-in dose escalation stage to establish the MTD or RP2D of FluCloXan and a Phase 2 expansion stage to determine efficacy and confirm safety of the FluCloXan regimen at the RP2D.
Principal Investigator Professor Arnon Nagler
Sponsor Race Oncology
Indication/population Adult men and women 18 to 65 years of age with relapsed and/ or refractory Acute Myeloid Leukemia (R/R AML) without central nervous extramedullary disease.
Number of Subjects Phase 1b: up to 12 patients in the dose determining phase
Phase 2: up to 17 patients in the expansion phase
Study Period 36 – 40 months
Study Design A two-cohort dose escalation schema using a standard 3 + 3 design will be employed followed by an expansion phase at the RP2D. As the patient population is considered relapsed and/or refractory to existing treatments, a comparator arm will not be used.
Statistical methods Simon 2 stage
End Points Primary
Phase 1b Dose Escalation: number of subjects experiencing a DLT in each cohort Phase 2 Expansion: Overall Response Rate (ORR) defined as the proportion of subjects with CR and CRi between Day 30 to Day 42 Secondary: Transplant/allo-HSCT rates (for transplant/allo-HSCT-eligible subjects); Combined CR and CRi and PR response rate; Morphologic leukemia-free state (MLFS); Partial remission (PR); Stable disease (SD); Progressive disease (PD); Relapse; Disease free survival (DFS); Overall survival (OS); Time to next treatment (for transplant/allo-HSCT-ineligible subjects); Molecular mutations including FTO overexpression status
Participating Centres 1 – Chaim Sheba Medical Center, Tel Hashomer, Israel
Start Date First patient in: Q3 CY2021
End Date Last patient In (anticipated): Q3 CY2023
Q&A
Will this trial support orphan drug registration of Bisantrene under the FDA 505(b)(2) pathway?
No. This trial uses an optimised drug combination discovered by the MD Anderson Cancer Center under a preclinical research project sponsored by Race Oncology. While this trial will not be used for FDA registration of Bisantrene, it will potentially provide oncologists with data on an optimal drug combination to use in the clinic.

Does this trial target FTO in AML patients?
No. While the trial is not FTO directed, the FTO expression status of the patients cancers in the trial will be determined to see if response correlates with FTO expression levels.

When can shareholders expect progress updates on the trial?
Q3 2021. The trial has received human ethics approval and Trialog has drug ready to supply in Israel. Prof Nagler’s team is highly skilled in treating AML and has recent experience using Bisantrene in AML patients. It is Race’s expectation that the first patient should be treated in the near future subject to recruitment. The Company will be updating our shareholders on progress at key points in the trial.

Why is this trial being run in Israel and not Australia or the USA?
AML has become a very competitive area to recruit patients as many companies are pursuing development of new drugs and treatments for R/R AML. It would not be possible to recruit patients for this combination treatment in Australia before 2024/25 because of competing trials. Prof Nagler’s personal experience using Bisantrene provides Race with a unique opportunity to run this trial now.

Will this trial be treating patients with extramedullary AML?
Yes. While the recently announced Australian AML trial will be exclusive to extramedullary AML patients, this trial will be open to all R/R AML patients including those with the extramedullary form of the disease. The only exception is those with CNS involvement as Bisantrene is not currently thought to cross into the brain and so would be likely be unsuitable for this patient population.

On June 22, 2021 ViiV Healthcare, the global specialist HIV company majority owned by GlaxoSmithKline plc ("GSK"), with Pfizer Inc. and Shionogi Limited as shareholders, and Halozyme Therapeutics, Inc. (Nasdaq: HALO) reported a global collaboration and license agreement that gives exclusive access to Halozyme’s ENHANZE drug delivery technology, recombinant human hyaluronidase PH20 enzyme (rHuPH20), for specific targets used in the treatment and prevention of HIV (Press release, Halozyme, JUN 22, 2021, View Source [SID1234584205]).

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Under the terms of the agreement, ViiV Healthcare will make an upfront payment of $40 million to Halozyme for the exclusive license to four HIV small and large molecule targets and is obligated to make potential future payments of up to $175 million in development and commercial milestones per target, subject to achievement of specified development and commercial milestones, including certain specified sales milestones. Halozyme will also be entitled to receive mid-single digit royalties on sales of commercialised medicines using the technology.

The PH20 enzyme breaks down a substance called hyaluronan (HA) that is found in the body’s subcutaneous space (under the skin) that acts as a barrier to the flow of fluid. By breaking down HA locally at the injection site and temporarily removing that barrier, large amounts of fluid can be injected into the subcutaneous space and dispersed. This facilitates the rapid delivery of large volume fluids by subcutaneous injection, potentially reducing the treatment burden of injectable drugs and providing optimised treatment options to patients. The HA is restored under the skin via normal processes within 24-48 hours.

Halozyme’s technology provides ViiV Healthcare with more opportunities to develop ultra-long acting medicines (dosing intervals of three months or longer) with its long-acting portfolio and pipeline products. Plans are underway to initiate the first experiments with the technology by the end of 2021 for investigational, long-acting cabotegravir for prevention of HIV, which is currently administered every two months.

"Many people living with HIV and those vulnerable to HIV tell us that for a variety of reasons, taking medicine every day is a challenge, and we have listened to them," said Kimberly Smith, M.D., MPH, Head of Research & Development at ViiV Healthcare. "We believe long-acting medicines are the future of HIV therapies and will help address these unmet needs. Our collaboration with Halozyme will keep us at the forefront of developing additional, innovative new options for HIV treatment and prevention as we work towards reducing the burden of HIV treatment."

"We are excited to partner with ViiV Healthcare to create new delivery options for innovative medicines for HIV," said Helen Torley, M.B. Ch. B., M.R.C.P., president and chief executive officer, Halozyme. "This collaboration demonstrates the potential value of our technology to facilitate rapid, large volume subcutaneous injections of not only more traditional medicines but also long-acting injectables, including small molecules, which in turn may further extend dosing intervals for people taking medicines for the treatment and prevention of HIV."

The license gives ViiV exclusive use of Halozyme’s proprietary rHuPH20 technology for four, specific HIV medicine targets that will expand opportunities for development of nearly all of ViiV’s pipeline assets. These assets are integrase inhibitors, reverse transcriptase inhibitors limited to nucleoside reverse transcriptase inhibitors (NRTI) and nucleoside reverse transcriptase translocation inhibitors (NRTTIs), capsid inhibitors and broadly neutralising monoclonal antibodies (bNAbs), that bind to the gp120 CD4 binding site.

Halozyme has licensed its technology to 11 pharmaceutical and biotechnology companies, for potential use in oncology, autoimmune disease, rare disease and infectious disease with products currently approved in oncology and immune deficiency indications. In addition, Halozyme currently has a Cooperative Research and Development Agreement with the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center in the US, which includes a bNAb, N6LS, that ViiV Healthcare licensed from the National Institutes of Health in 2019.