On October 17, 2019 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), ("Onxeo" or "the Company"), a clinical-stage biotechnology company specializing in the development of innovative drugs targeting tumor DNA Damage Response (DDR) in oncology, in particular against rare or resistant cancers, reported that the Company has signed a collaboration agreement with the French State and the Île-de-France Region as part of the Innov’up Leader program PIA (Program of Investments for the Future) with funding of €495,000 (Press release, Onxeo, OCT 17, 2019, View Source [SID1234542331]).

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The programme, funded in equal amounts by the State and the Region, aims to accelerate the emergence of future leaders in their market who can claim international scope and are the driving force of disruptive innovation projects.

The winning project of Onxeo involves the development of a drug candidate targeting new therapeutic targets in immuno-oncology. Derived from the platON platform, it will be based on the principle of a decoy agonist oligonucleotide, as AsiDNA is. The sum of €495,000, granted by public partners to the co-financing, represents 50% of the total amount of the project and consists of a grant of €330,000 and a repayable advance of €165,000. It is paid in two instalments, with a first payment upon signing of the contract.

"We are very pleased with this funding, which will allow us to accelerate the expansion of our pipeline of drug candidates. With this project, we capitalize on our expertise in the field of DDR and decoy-oligonucleotide drugs, while targeting the very attractive and booming field of immuno-oncology." stated Judith Greciet, Chief Executive Officer of Onxeo.

On October 17, 2019 AIVITA Biomedical, Inc., a biotechnology company specializing in innovative stem cell applications, reported the publication of an article titled "Survival Comparison between Melanoma Patients Treated with Patient-Specific Dendritic Cell Vaccines and Other Immunotherapies Based on Extent of Disease at the Time of Treatment" in the journal Biomedicines. Robert O. Dillman, M.D., Chief Medical Officer at AIVITA, and Candace Hsieh, Ph.D., Vice President, Clinical Development & Regulatory Affairs at AIVITA, authored the article (Press release, AIVITA Biomedical, OCT 17, 2019, View Source [SID1234542332]).

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The article reported that superior survival was observed in patients treated with AIVITA’s immunotherapy targeting tumor-initiating cells. Accounting for clinical stage and extent of tumor at the time of treatment, survival was best in patients classified as recurrent stage 3 without measurable disease. Next best was in patients classified as stage 4 without measurable disease, followed by measurable stage 4 disease.

Survival of the patients was compared to the best contemporary controls from the clinical trial literature. Even though contemporary controls typically had better prognostic features, median and/or long-term survival was consistently better in patients treated with AIVITA’s immunotherapy. It was noted that there is a strong rationale for combining AIVITA’s product with anti-PD-1 in the treatment of patients with metastatic melanoma.

"Because the survival results with AIVITA’s immunotherapy were so good, colleagues have constantly questioned the stage and extent of disease in these patients, and asked for comparisons to patients from other trials," said Dr. Robert O. Dillman, Chief Medical Officer at AIVITA. "Our analyses confirm superior survival while accounting for clinical stage and extent of disease, supporting expansion into additional cancer types."

AIVITA is currently conducting three independent clinical studies investigating its platform immunotherapy in patients with ovarian cancer, glioblastoma and melanoma. AIVITA uses 100% of proceeds from the sale of its ROOT of SKIN skincare line to support the treatment of women with ovarian cancer.

CLINICAL TRIAL DETAIL

OVARIAN CANCER

AIVITA’s ovarian Phase 2 double-blind study is active and enrolling approximately 99 patients who are being randomized in a 2:1 ratio to receive either the autologous cancer stem cell-targeting immunotherapy or autologous monocytes as a comparator.

Patients eligible for randomization and treatment will be those (1) who have undergone debulking surgery, (2) for whom a cell line has been established, (3) who have undergone leukapheresis from which sufficient monocytes were obtained, (4) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), and (5) who have completed primary therapy. The trial is not open to patients with recurrent ovarian cancer.

For additional information about AIVITA’s AVOVA-1 trial patients can visit: www.clinicaltrials.gov/ct2/show/NCT02033616

GLIOBLASTOMA

AIVITA’s glioblastoma Phase 2 single-arm study is active and is enrolling approximately 55 patients to receive the cancer stem cell-targeting immunotherapy.

Patients eligible for treatment will be those (1) who have recovered from surgery such that they are about to begin concurrent chemotherapy and radiation therapy (CT/RT), (2) for whom an autologous tumor cell line has been established, (3) have a Karnofsky Performance Status of > 70 and (4) have undergone successful leukapheresis from which peripheral blood mononuclear cells (PBMC) were obtained that can be used to generate dendritic cells (DC). The trial is not open to patients with recurrent glioblastoma.

For additional information about AIVITA’s AV-GBM-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03400917

MELANOMA

AIVITA’s melanoma Phase 1B open-label, single-arm study will establish the safety of administering anti-PD1 monoclonal antibodies in combination with AIVITA’s cancer stem cell-targeting immunotherapy in patients with measurable metastatic melanoma. The study will also track efficacy of the treatment for the estimated 14 to 20 patients. This trial is not yet open for enrollment.

Patients eligible for treatment will be those (1) for whom a cell line has been established, (2) who have undergone leukapheresis from which sufficient monocytes were obtained, (3) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), (4) who have either never received treatment for metastatic melanoma or were previously treated with enzymatic inhibitors of the BRAF/MEK pathway because of BRAF600E/K mutations and (5) are about to initiate anti-PD1 monotherapy.

For additional information about AIVITA’s AV-MEL-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03743298

On October 17, 2019 OncoCyte reported that it has entered into a First Amendment to Loan and Security Agreement (the "Amended Loan Agreement") with Silicon Valley Bank (the "Bank") pursuant to which Oncocyte obtained a new $3 million secured credit facility ("Tranche 1"), a portion of which was used to repay the remaining balance of approximately $400,000 on outstanding loans from the Bank, plus a final payment of $116,000, under the February 21, 2017 Loan Agreement with the Bank (Filing, 8-K, Oncocyte, OCT 17, 2019, View Source [SID1234551120]). The credit line under the Amended Loan Agreement may be increased by an additional $2 million ("Tranche 2") if OncoCyte obtains at least $20 million of additional equity capital, as was the case with the original Loan Agreement, and a positive final coverage determination is received from the Centers for Medicate and Medicaid Services for the Razor lung cancer test at a specified minimum price point per test (the "Tranche 2 Milestone"), and OncoCyte is not in default under the Amended Loan Agreement.

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Payments of interest only on the principal balance will be due monthly from the draw date through March 31, 2020 followed by 24 monthly payments of principal and interest, provided, however, that if the Tranche 2 Milestone is achieved the interest only payment period will be extended through September 30, 2020 followed by 18 equal monthly payments of principal plus interest. The outstanding principal balance of the loan will bear interest at a stated floating annual interest equal to (a) the greater of 0.75% above the prime rate or 4.25% for Tranche 1 loans, or (b) the greater of the prime rate or 5% per annum for Tranche 2 loans.

The principal amount of all loans plus accrued interest will be due and payable to the Bank at maturity on March 31, 2022. At maturity, OncoCyte will also pay the Bank an additional final payment fee of $200,000. Any amounts borrowed and repaid may not be reborrowed.

OncoCyte may prepay in full the outstanding principal balance at any time, subject to a prepayment fee equal to 3.0% of the outstanding principal balance if prepaid within one year after October 17, 2019, 2.0% of the outstanding principal balance if prepaid more than one year but less than two years after October 17, 2019, or 1.0% of the outstanding principal balance if prepaid two years or more after October 17, 2019.

The outstanding principal amount of the loan, with interest accrued, the final payment fee, and the prepayment fee may become due and payable prior to the applicable maturity date if an "Event of Default" as defined in the Amended Loan Agreement occurs and is not cured within any applicable cure period. An Event of Default includes, among other events, failure to pay interest and principal when due, material adverse changes, which include a material adverse change in OncoCyte’s business, operations, or condition (financial or otherwise), failure to provide the bank with timely financial statements and filings with the Securities and Exchange Commission, as required, legal judgments or pending or threatened legal actions of $50,000 or more, insolvency, and delisting from the NYSE American. OncoCyte’s obligations under the Amended Loan Agreement are collateralized by substantially all of its assets other than intellectual property such as patents and trade secrets that OncoCyte owns.

On October 17, 2019 in conjunction with Tranche 1 becoming available under the Amended Loan Agreement, OncoCyte issued a common stock purchase warrant to the Bank (the "Bank Warrant") entitling the Bank to purchase 98,574 shares of OncoCyte common stock at the initial Warrant Price of $1.69 per share through October 17, 2029. The number of shares of common stock issuable upon the exercise of the Bank Warrant will increase on the date of each draw, if any, on Tranche 2. The number of additional shares of common stock issuable upon the exercise of the Bank Warrant will be equal to 0.02% of OncoCyte’s fully diluted equity outstanding for each $1 million draw under Tranche 2. The Warrant Price for Tranche 2 warrant shares will be determined upon each draw of Tranche 2 funds and will be closing price of OncoCyte common stock on the NYSE American or other applicable market on the date immediately before the applicable date on which OncoCyte borrows funds under Tranche 2. The Bank may elect to exercise the Bank Warrant on a "cashless exercise" basis and receive a number of shares determined by multiplying the number of shares for which the Bank Warrant is being exercised by (A) the excess of the fair market value of the common stock over the applicable Warrant Price, divided by (B) the fair market value of the common stock. The fair market value of the common stock will be last closing or sale price on a national securities exchange, interdealer quotation system, or over-the-counter market.

On October 17, 2019 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported an update on its portfolio of selective cyclin-dependent kinase 7 (CDK7) inhibitors (Press release, Syros Pharmaceuticals, OCT 17, 2019, View Source [SID1234542333]). The Company has decided to prioritize the development of its highly selective and potent oral CDK7 inhibitor, SY-5609, and to discontinue further development of SY-1365, its intravenous (IV) CDK7 inhibitor. Syros expects to initiate a Phase 1 clinical trial of SY-5609 in patients with select solid tumors in the first quarter of 2020.

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SY-5609 inhibits CDK7 more selectively and potently than SY-1365 and has demonstrated greater anti-tumor activity than SY-1365 in multiple preclinical models. Furthermore, initial clinical activity and tolerability data from the expansion of the Phase 1 trial of SY-1365 did not support an optimal profile for patients, particularly in light of an increasing focus on oral targeted agents in cancer. As an oral molecule, Syros believes SY-5609 provides more flexibility in dosing and greater opportunity to sustain the levels of target coverage needed to improve treatment outcomes. Based on these factors, Syros has made a CDK7 portfolio decision to focus on SY-5609.

"We believe in selective CDK7 inhibition as a potentially transformative targeted approach for difficult-to-treat cancers," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "SY-1365 was the first selective CDK7 inhibitor to enter clinical development, demonstrating proof-of-mechanism for this novel therapeutic approach and showing early signs of clinical activity. We have gained important insights from our work on SY-1365 that have informed our development strategy for SY-5609, including focusing on patient populations most likely to respond to a CDK7 inhibitor. We are prioritizing SY-5609 because we believe it has best-in-class potential and that it provides the greatest opportunity to realize the promise of selective CDK7 inhibition for patients."

SY-5609: An Oral, Highly Selective and Potent Non-Covalent CDK7 Inhibitor

SY-5609 has induced deep and sustained tumor growth inhibition, including complete regressions, in preclinical models of breast, ovarian and lung cancers at doses below the maximum tolerated dose. SY-5609 has also shown substantial anti-tumor activity in combination with fulvestrant in hormone receptor (HR)-positive breast cancer models that are resistant to CDK4/6 inhibitors. Importantly, SY-5609 showed greater tumor growth inhibition than SY-1365 in preclinical models in which they were both studied, including those that were not responsive to SY-1365.

Syros is on track to complete investigational new drug application-enabling studies for SY-5609 by year-end. The Company expects to initiate a Phase 1 trial in patients with select solid tumors, including breast, lung and ovarian cancers and cancers of any histology defined by a specific molecular signature, in the first quarter of 2020. Syros plans to present new preclinical data on the pharmacokinetics, pharmacodynamics and anti-tumor activity of SY-5609 on October 29 at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston. The abstract for the presentation is available on the conference website at: View Source

Initial data from expansion portion of Phase 1 trial of SY-1365

As of a planned September 30 data snapshot, 68 patients had been treated in the expansion portion of the Phase 1 trial of SY-1365, including 53 across the single-agent cohorts in patients with high-grade serous ovarian cancer (HGSOC), relapsed clear cell ovarian cancer and solid tumors of any histology available for biopsy, and 15 patients in the combination cohorts in HGSOC and metastatic CDK4/6 inhibitor-resistant HR-positive breast cancer.

Syros initiated the single-agent expansion cohorts at a dose of 80 mg/m2 twice weekly and the combination cohorts at 53 mg/m2 once weekly. During the expansion, peri-infusional adverse events (AEs) thought to be related to the IV administration of SY-1365 prompted evaluations of lower doses in the single-agent cohorts and extended infusion times across all the cohorts. Extended infusion times reduced peak drug concentrations and appeared to reduce the overall frequency and severity of peri-infusional AEs, including headache, nausea and vomiting.

The best response observed across the expansion cohorts was stable disease, as defined by RECIST criteria. Response-evaluable patients were primarily treated at doses of 53 and 64 mg/m2. Of the 31 response-evaluable patients treated with single-agent SY-1365, 13 (42 percent) had stable disease. Of the 11 response-evaluable patients treated in the combination cohorts, seven (64 percent) had stable disease.

Based on preclinical and clinical data, Syros believes that sustaining the level of CDK7 target coverage needed to enhance clinical activity would require more frequent dosing, or a higher dose that would necessitate further lengthening the infusion to manage tolerability. Syros believes that either approach could create an overly burdensome dosing schedule for patients that can better be addressed with SY-5609.

Conference Call and Webcast:

Syros will host a conference call at 8:30 a.m. ET today to discuss this update on its CDK7 franchise and plans to prioritize the development of SY-5609.

To access the live call, please dial 866-595-4538 (domestic) or 636-812-6496 (international) and refer to conference ID 4578949. A webcast of the call will also be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay will be available for approximately 30 days following the call.

On October 17, 2019 Allergan plc (NYSE: AGN) reported it will release third quarter 2019 financial results on Tuesday, November 5, 2019, prior to the open of U.S. financial markets (Press release, Allergan, OCT 17, 2019, View Source [SID1234542335]).

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Allergan plc logo

For additional materials related to Allergan’s third quarter results, please visit Allergan’s Investor Relations website at View Source