On December 12, 2019 Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) ("Ionis") reported that it has entered into privately negotiated exchange and/or subscription agreements, with certain holders of its outstanding 1.00% Convertible Senior Notes due 2021 (the "2021 Notes") and certain new investors pursuant to which Ionis will issue $398.0 million principal amount of 0.125% Convertible Senior Notes due 2024 (the "New Notes") in exchange for $340.2 principal amount of the 2021 Notes (the "Exchange Transactions") and issue $109.5 million principal amount of New Notes for cash (the "Subscription Transactions") (Press release, Ionis Pharmaceuticals, DEC 12, 2019, View Source;300973802.html [SID1234552335]). Following the closing of the Exchange Transactions, $344.8 million in aggregate principal amount of 2021 Notes will remain outstanding with terms unchanged. The Exchange Transactions and the Subscription Transactions are expected to close concurrently on or about December 19, 2019, subject to customary closing conditions.

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The New Notes will represent senior unsecured obligations of Ionis and will pay interest semi-annually in arrears on each June 15 and December 15, commencing on June 15, 2020, at a rate of 0.125% per annum. The New Notes will mature on December 15, 2024, unless earlier converted or repurchased. The New Notes will be convertible at the option of the holders in certain circumstances into cash, shares of Ionis’ common stock or a combination of cash and Ionis’ common stock, at Ionis’ election. The initial conversion rate is 12.0075 shares of Ionis’ common stock per $1,000 principal amount of New Notes, which is equivalent to an initial conversion price of approximately $83.28 per share, and will be subject to customary anti-dilution adjustments. Ionis may not redeem the New Notes prior to the maturity date.

Ionis will not receive any cash proceeds from the Exchange Transactions. In exchange for issuing the New Notes pursuant to the Exchange Transactions, Ionis will receive and cancel the exchanged 2021 Notes. Ionis estimates that net cash proceeds from the Subscription Transactions will be approximately $99.2 million after deducting estimated offering expenses for both the Exchange Transactions and the Subscription Transactions. Ionis intends to use net cash proceeds from the Subscription Transactions to pay the cost of the convertible note hedge transaction described below and for general corporate purposes.

In connection with the exchange and/or subscription agreements, Ionis entered into convertible note hedge and warrant transactions with several financial institutions. These transactions may decrease or increase dilution of Ionis’ stock based on several factors that are outlined in further detail in the Company’s 8-K filing, which was filed contemporaneously with this press release.

The New Notes and any shares of common stock issuable upon conversion of the New Notes have not been registered under the Securities Act or under any state securities laws and may not be offered or sold without registration under, or an applicable exemption from, the registration requirements. This announcement does not constitute an offer to sell, nor is it a solicitation of an offer to buy, these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any state or any jurisdiction.

On December 12, 2019 Biocept, Inc. (NASDAQ: BIOC) ("Biocept" or the "Company"), a leading commercial provider of liquid biopsy solutions, reported that on December 11, 2019 it closed its previously announced underwritten public offering of 24,600,000 shares of its common stock (or pre-funded warrants to purchase common stock in lieu thereof) and warrants to purchase up to 24,600,000 shares of its common stock (Press release, Biocept, DEC 12, 2019, View Source [SID1234552334]). Each share of common stock or pre-funded warrant was sold together with one warrant to purchase one share of common stock at a combined price to the public of $0.405 per share and warrant. Gross proceeds, before underwriting discounts and commissions and estimated offering expenses, were approximately $10.0 million. In addition, Biocept granted to Maxim Group LLC a 45-day option to purchase up to an additional 3,690,000 shares of common stock and/or warrants to purchase up to 3,690,000 shares of common stock, at the public offering price less discounts and commissions, of which Maxim Group LLC has partially exercised its option to purchase warrants to purchase up to 1,927,500 shares of common stock.

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The warrants are immediately exercisable at a price of $0.405 per share of common stock and will expire five years from the date of issuance. Additionally, if the volume-weighted average price of our common stock is below the exercise price per share of the warrants on any trading day beginning the earlier of (i) January 8, 2020, and (ii) the trading day on which the aggregate trading volume of Biocept’s common stock is equal to more than three times the number of shares of common stock sold in the offering, then the warrantholders may elect to cashless exercise their warrants for a number of shares equal to 50% of the shares issuable upon cash exercise. Each pre-funded warrant has an exercise price of $0.01 per share, is exercisable immediately and will expire when exercised in full. The shares of common stock or the pre-funded warrants and the accompanying warrants, were sold together in the offering, but were issued separately and were immediately separable upon issuance.

Maxim Group LLC acted as the book-running manager and Dawson James Securities, Inc. acted as a co-manager in connection with the offering.

The offering was conducted pursuant to the Company’s registration statement on Form S-1 (File No. 333-234459), as amended, previously filed with and subsequently declared effective by the Securities and Exchange Commission ("SEC"). A final prospectus relating to the offering has been filed with the SEC and is available on the SEC’s website at View Source Electronic copies of the final prospectus relating to this offering may be obtained from Maxim Group LLC, 405 Lexington Avenue, 2nd Floor, New York, NY 10174, at (212) 895-3745.

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

On December 12, 2019 Medicenna Therapeutics Corp. ("Medicenna" or "the Company") (TSX: MDNA,OTCQB: MDNAF), a clinical stage immuno-oncology company, reported updated clinical results from its Phase 2b trial of MDNA55, in patients with recurrent glioblastoma (rGBM), the most common and uniformly fatal form of brain cancer (Press release, Medicenna Therapeutics, DEC 12, 2019, View Source [SID1234552333]). The results were presented by Dr. Fahar Merchant, PhD, President and CEO of Medicenna Therapeutics, at the Inaugural Glioblastoma Drug Development Annual Summit on December 11 at the Westin Boston Waterfront Hotel in Boston, Massachusetts.

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The presentation reported subgroup analysis from the first 40 patients treated with MDNA55 in a Phase 2b clinical trial for patients with rGBM. MDNA55 targets the interleukin 4 receptor (IL4R) known to be over-expressed in GBM, and a biomarker for more aggressive disease. Furthermore, unlike other trials, the MDNA55 study only enrolled patients with rGBM that have genetic features which make the tumor the most aggressive and resilient type of rGBM.

"We are very encouraged to see that by being the only oncology company to target the IL4R, which is over-expressed in 76% of patients with glioblastoma, we are achieving meaningful survival benefits with MDNA55 in a population where the majority of patients have the worst form of rGBM," said Dr. Fahar Merchant, President and CEO of Medicenna. "Our full data set will be complete early in the new year, allowing us to submit our package to the U.S. Food and Drug Administration in Q1, 2020 prior to an End of Phase 2 Meeting enabling us to reach a major milestone on the path to securing key partnerships."

The presentation highlighted that the patient characteristics in the clinical study excluded patients that are known to have a much better prognosis, such as patients that were, (a) eligible for surgery to remove the tumor, (b) had a lower grade of brain cancer at initial diagnosis (only de novo GBM patients were enrolled), and (c) had a known mutation associated with better prognosis (IDH mutation). Furthermore, the presentation emphasized that despite enrolling only patients known to have a very poor prognosis, patients actually did much better and were surviving significantly longer following only one treatment with MDNA55, particularly in patients with high expression of the IL4R target.

Of particular interest, subjects receiving lower doses of steroids (≤ 4mg of concurrent steroid per day) showed a trend towards improved survival, particularly in the IL4R High group, with a median overall survival (mOS) of 16.5 months with 88% of patients being still alive at 12 months. In patients resistant to approved chemotherapy Temodar (rGBM with unmethylated MGMT promoter), MDNA55 treatment in IL4R High patients had a median overall survival of 15.2 months and a 12 month survival rate of 69% versus 22% for Lomustine and less than 19% for Avastin.

Additional data comparing the various prognostic factors on MDNA55 outcome measures are provided in the slide presentation available on-line at View Source

On December 12, 2019 Agendia, Inc., a world leader in precision oncology for breast cancer, reported new data comparing genomic profiling results for patients under the age of 50 with early-stage breast cancer (Press release, Agendia, DEC 12, 2019, View Source [SID1234552332]). The data, which are being presented for the first time today at the 2019 San Antonio Breast Cancer Symposium (SABCS), show that the MammaPrint 70-gene assay may more effectively identify premenopausal women who may safely avoid chemotherapy.

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One of the biggest challenges physicians face when treating patients with early stage, curable breast cancer is choosing a treatment path that will mitigate the risk of disease recurrence, while avoiding over- or undertreatment. Genomic profiling has helped address this clinical need, but recent findings suggest age may impact the veracity of results for some assays. A follow up to the TAILORx study published in 2018 led to a change in recurrence score (RS) stratification for patients under 50 and, more importantly, left the ideal treatment plan for those with a RS of 21-25 unclear.

"Understanding how patient age may affect possible benefit from chemotherapy is a critically important question that has needed further exploration and clarification," said William Audeh, MD, MS, chief medical officer, Agendia.

The Agendia Prospective Study of MammaPrint in Breast Cancer Patients with an Intermediate Recurrence Score (PROMIS) trial previously demonstrated that MammaPrint, which provides a binary, High Risk or Low Risk of recurrence, delivers clinically actionable results for patients who receive a RS of 18-30 by the 21-gene assay. The findings presented today at SABCS represent a sub-analysis of the PROMIS data, which Agendia conducted to help determine the potential of the MammaPrint test to clarify adjuvant chemotherapy decisions for premenopausal women.

Results – which are statistically significant – demonstrate that 58 percent of women age 50 and under with RS 18-20 and 46 percent of those with RS 21-25 are categorized as MammaPrint Low, indicating that they may safely forgo chemotherapy. Additionally, 15 percent of women with RS 26-30 were found to be MammaPrint Low Risk and may be potential candidates for de-escalation of adjuvant chemotherapy.

"Treatment recommendations in ER+ patients <50 years: Comparison of the 21-gene assay and 70-gene signature in the PROMIS study" can be found at: View Source

On December 12, 2019 Senhwa Biosciences Inc. (TPEx: 6492), a clinical stage biopharmaceutical company focused on next generation DNA Damage Response (DDR) therapeutics for the treatment of cancer, reported positive results from its Phase 1 trial of CX-5461. CX-5461 is the company’s First-in-Class G-quadruplex stabilizer (Press release, Senhwa Biosciences, DEC 12, 2019, View Source [SID1234552331]). The patients enrolled in the study all presented with advanced solid tumors, with no other available treatment options.

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In 2016, CX-5461 was awarded a Stand Up to Cancer Dream Team Grant. Phase 1 clinical findings were featured within a spotlighted presentation at the annual 2019 San Antonio Breast Cancer Symposium (SABCS) by Senhwa’s clinical partner, Canadian Cancer Trials Group (CCTG).

"CX-5461 has demonstrated clinically meaningful and durable benefits in patients with specific tumor biomarkers that are also resistant to platinum and other chemotherapeutics. The Phase 1 study has validated CX-5461 as a G-quadruplex stabilizer within a novel class of therapy that accelerates dsDNA breaks and has proven human efficacy across certain tumor types," said Dr. Tai-Sen Soong, CEO of Senhwa Biosciences. The clinical results exhibited that CX-5461 has the potential to rescue cancer patients who have developed resistance to platinum and other chemotherapeutics. Additional clinical trials are being planned to further confirm the efficacy seen.

The Phase 1 dose escalation portion of the CX-5461 trial was designed to determine Recommended Phase 2 Dose (RP2D), as well as evaluate preliminary anti-tumor activity of a single agent (CX-5461), in patients with metastatic and recurrent solid tumors. 41 patients enrolled in the study, due to the fact that all available treatments had failed to treat their malignancies, and 40 of those patients had been treated with different dose levels of CX-5461.

As of the November 25th, 2019 data cutoff, the study findings showed:

32 of 41 patients enrolled were evaluable patients, the median age was 53 (range 25-73).
Of the evaluable patients, 24 had attempted 3 or more prior treatment regimens for their disease.
In this heavily pre-treated Phase 1 population, responses were seen with CX-5461 within the dose range of 100mg/m2 to 650mg/m2.
Patients presented with a range of solid tumors, including metastatic breast cancer (47.5%), Ovary (17.5%), Pancreas (7.5%), Non-small-cell Lung Cancer (5%) and others (22.5%)
Preliminary Safety Analysis:

CX-5461 was well tolerated:
– Treatment-related Adverse Events (AEs ≥20%) were photosensitivity of the skin (58%); eye disorders (including Photosensitivity 20%); nausea (70%); headache (25%); fatigue (73%).
– No Dose Limited Toxicities (DLTs) observed to date. There were 6 treatment-related non-DLT grade 3 photosensitivity events.
– The RP2D was determined to be 475mg/m2 on days 1, 8 and 15 of a 4-week cycle.
UV avoidance and protection measures were successful in mitigating risks associated with photo toxicity.
Preliminary Efficacy Analysis:

As of the data cutoff, 32 patients were evaluable for response. In terms of best response, 4 patients (3 breast cancer, 1 ovary) had a confirmed Partial Response with an additional 4 patients had durable Stable Disease.
Heavily pre-treated (including platinum resistant) patients with specific biomarkers showed significant tumor shrinkage and maintained significant treatment duration in the trial. The maximum duration was 16 cycles, with 28 days per cycle.
G-quadruplex stabilizers are a novel class of therapy that has demonstrated accelerated dsDNA breaks.
About CX-5461

CX-5461 is designed to stabilize DNA G-quadruplexes of cancer cells and leads to disruption of the cell’s replication fork. While acting in concert with HR (Homologous Recombination) pathway deficiency, such as BRCA1/2 mutations, replication forks stall and cause DNA breaks, resulting in cancer cell death. CX-5461 in combination with HRD (Homologous Recombination Deficiency) tumors may be exploited through a synthetic lethality approach, targeting DNA repair defects in HRD tumors.