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Salarius Pharmaceuticals and Aspire Capital Announce a $10.9M Common Stock Purchase Agreement

On October 28, 2019 Salarius Pharmaceuticals, Inc. (Nasdaq: SLRX), a clinical-stage oncology company targeting the epigenetic causes of cancers, reported that it has entered into a $10.9 million common stock purchase agreement, including a $1.0 million initial common stock purchase, with Aspire Capital Fund, LLC, a Chicago-based institutional investor (Press release, Salarius Pharmaceuticals, OCT 28, 2019, View Source [SID1234549922]).

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With the investment by Aspire plus non-dilutive funding from the Cancer Prevention Research Institute of Texas (CPRIT) and ongoing financial support from the National Pediatric Cancer Foundation, Salarius believes it is well-capitalized to advance its current clinical programs through a number of near-term, value creating milestones, including early safety and efficacy data readouts from the ongoing Phase 1/2 clinical trial of Seclidemstat, Salarius’ lead drug candidate, in Ewing sarcoma and the Phase 1 clinical trial of Seclidemstat in advanced solid tumors.

Under the agreement, Aspire Capital is committed to purchase up to $10.9 million of Salarius’ common stock over a 30-month span extending into 2022, subject to certain terms and conditions. Immediately upon execution of the agreement, Aspire Capital made an initial purchase of 210,526 shares for $1.0 million, a per share purchase price of $4.75, which is equal to the closing sale price of Salarius’ shares on October 24, 2019, the date of the agreement. Any additional sales to Aspire Capital under the agreement will occur at the sole discretion of Salarius and at prices based on the market price of Salarius’ common stock at the time of each sale.

"This common stock purchase agreement with Aspire Capital provides Salarius with additional access to capital and financing flexibility allowing Salarius to further advance its lead drug candidate, Seclidemstat," commented David Arthur, Chief Executive Officer of Salarius. "We believe our non-dilutive financial support from both CPRIT and the National Pediatric Cancer Foundation, now combined with funding from Aspire Capital, puts Salarius in a good financial position as we continue our work targeting the epigenetic causes of cancer."

Steven G. Martin, the Managing Member of Aspire Capital, commented, "We are very pleased to announce this investment in Salarius as we recognize LSD1 as a novel and exciting target with ever increasing clinical validation in a broad range of cancers, including Ewing sarcoma and other advanced solid tumors, as well as hematologic cancers such as AML. Seclidemstat has demonstrated promising and potentially best-in-class characteristics driven by its differentiated reversible binding profile and inhibition of both the enzymatic and scaffolding functions of LSD1. Furthermore, we’re intrigued by recent evidence showing that the inhibition of LSD1 stimulates interferon production highlighting Seclidemstat’s potential as an important new immuno-oncology agent. Aspire Capital is confident that Salarius offers a good opportunity for near and long-term value creation."

Under the terms of the agreement with Aspire Capital, Salarius retains full control over the timing of any stock sales made under the agreement and the amount of stock sold to Aspire Capital. There are no warrants, options, financing swaps, derivatives or other securities associated with the agreement. The agreement contains no restrictions on the use of proceeds, financial covenants or restrictions on future financings and no rights of first refusal, participation rights, penalties or liquidated damages. Lastly, Salarius maintains the right to terminate the agreement at any time, at its discretion, without any additional cost or penalty. The proceeds from this agreement will be used for working capital and general corporate purposes.

In addition to the Common Stock Purchase Agreement, Salarius also entered into a Registration Rights Agreement with Aspire Capital. Additional details regarding the transaction, including the issuance of commitment fee shares, the Common Stock Purchase Agreement and related Registration Rights Agreement is available in Salarius’ Current Report on Form 8-K, filed today with the SEC. Salarius has filed a prospectus supplement to its Form S-3 shelf registration statement (File No. 333-231010), which was declared effective on May 17, 2019 by the U.S. Securities and Exchange Commission, qualifying the offer and sale of common shares to Aspire Capital. A copy of the Prospectus Supplement is available on EDGAR at www.sec.gov or may be obtained upon request to Salarius. 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 jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of such jurisdiction.

Entry into a Material Definitive Agreement

On October 28, 2019, Celsion Corporation (the "Company"), reported that it entered into a common stock purchase agreement (the "Purchase Agreement") with Aspire Capital Fund, LLC, an Illinois limited liability company ("Aspire Capital") which provides that, upon the terms and subject to the conditions and limitations set forth therein, Aspire Capital is committed to purchase up to an aggregate of $10.0 million of shares of the Company’s common stock over the 24-month term of the Purchase Agreement (Filing, 8-K, Celsion, OCT 28, 2019, View Source [SID1234549921]). Concurrently with entering into the Purchase Agreement, the Company also entered into a registration rights agreement with Aspire Capital (the "Registration Rights Agreement"), in which the Company agreed to file one or more registration statements, as permissible and necessary to register under the Securities Act of 1933, as amended (the "Securities Act"), registering the sale of the shares of the Company’s common stock that have been and may be issued to Aspire Capital under the Purchase Agreement.

Under the Purchase Agreement, after the Securities and Exchange Commission (the "SEC") has declared effective the registration statement referred to above, on any trading day selected by the Company, the Company has the right, in its sole discretion, to present Aspire Capital with a purchase notice (each, a "Purchase Notice"), directing Aspire Capital (as principal) to purchase up to 100,000 shares of the Company’s common stock per business day, up to $10.0 million of the Company’s common stock in the aggregate at a per share price (the "Purchase Price") equal to the lesser of:

the lowest sale price of the Company’s common stock on the purchase date; or
the arithmetic average of the three (3) lowest closing sale prices for the Company’s common stock during the ten (10) consecutive trading days ending on the trading day immediately preceding the purchase date.

In addition, on any date on which the Company submits a Purchase Notice to Aspire Capital in an amount of 100,000 shares, the Company also has the right, in its sole discretion, to present Aspire Capital with a volume-weighted average price purchase notice (each, a "VWAP Purchase Notice") directing Aspire Capital to purchase an amount of stock equal to up to 30% of the aggregate shares of the Company’s common stock traded on its principal market on the next trading day (the "VWAP Purchase Date"), subject to a maximum number of shares the Company may determine. The purchase price per share pursuant to such VWAP Purchase Notice is generally 97% of the volume-weighted average price for the Company’s common stock traded on its principal market on the VWAP Purchase Date.

The Purchase Price will be adjusted for any reorganization, recapitalization, non-cash dividend, stock split, or other similar transaction occurring during the period(s) used to compute the Purchase Price. The Company may deliver multiple Purchase Notices and VWAP Purchase Notices to Aspire Capital from time to time during the term of the Purchase Agreement, so long as the most recent purchase has been completed.

The Purchase Agreement provides that the Company and Aspire Capital shall not effect any sales under the Purchase Agreement on any purchase date where the closing sale price of the Company’s common stock is less than $0.25. There are no trading volume requirements or restrictions under the Purchase Agreement, and the Company will control the timing and amount of sales of the Company’s common stock to Aspire Capital. Aspire Capital has no right to require any sales by the Company, but is obligated to make purchases from the Company as directed by the Company in accordance with the Purchase Agreement. There are no limitations on use of proceeds, financial or business covenants, restrictions on future fundings, rights of first refusal, participation rights, penalties or liquidated damages in the Purchase Agreement. In consideration for entering into the Purchase Agreement, concurrently with the execution of the Purchase Agreement, the Company issued to Aspire Capital 100,000 shares of the Company’s common stock (the "Commitment Shares"). The Purchase Agreement may be terminated by the Company at any time, at its discretion, without any cost to the Company. Aspire Capital has agreed that neither it nor any of its agents, representatives and affiliates shall engage in any direct or indirect short-selling or hedging of the Company’s common stock during any time prior to the termination of the Purchase Agreement. Any proceeds from the Company receives under the Purchase Agreement are expected to be used for working capital and general corporate purposes.

The foregoing is a summary description of certain terms of the Purchase Agreement and the Registration Rights Agreement and, by its nature, is incomplete. Copies of the Purchase Agreement and Registration Rights Agreement are filed herewith as Exhibits 10.1 and 4.1, respectively, to this Current Report on Form 8-K and are incorporated herein by reference. All readers are encouraged to read the entire text of the Purchase Agreement and the Registration Rights Agreement.

The issuance of the Commitment Shares and all other shares of common stock that may be issued from time to time to Aspire Capital under the Purchase Agreement is exempt from registration under the Securities Act, pursuant to the exemption for transactions by an issuer not involving any public offering under Section 4(a)(2) of the Securities Act.

MIRATI THERAPEUTICS PRESENTS FIRST CLINICAL DATA OF PHASE 1/2 TRIAL OF MRTX849 AT THE 2019 AACR-NCI-EORTC INTERNATIONAL CONFERENCE ON MOLECULAR TARGETS AND CANCER THERAPEUTICS

On October 28, 2019 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported the first clinical results from its Phase I/2 trial evaluating MRTX849, an investigational KRAS G12C inhibitor, in patients with solid tumors expressing KRAS G12C mutations (Press release, Mirati, OCT 28, 2019, View Source [SID1234549920]). MRTX849 demonstrated clinical activity, including objective responses, in patients with non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). While the maximum tolerated dose (MTD) has not yet been established, dose expansion is underway, and the trial continues to enroll patients. These data were presented in an oral presentation at the 2019 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.

"Patients whose tumors carry the KRAS G12C mutation have a poor prognosis, are resistant to standard of care treatment and have no available targeted therapeutic options," said Charles M. Baum, M.D., Ph.D., President and Chief Executive Officer, Mirati Therapeutics. "Early efficacy and safety data from this Phase 1/2 trial demonstrate the potential of a potent and effective KRAS therapy. We look forward to investigating MRTX849 in patients with a variety of KRAS G12C mutated cancers and bringing the hope of a targeted therapy to them."

The ongoing Phase 1/2, first-in-human, open-label multicenter trial has enrolled 17 patients, including 10 patients with NSCLC, 4 patients with CRC, and 3 patients with other tumor types. Five dose cohorts have been evaluated: 150 mg, 300 mg, 600 mg, and 1200 mg, taken orally once daily, and 600 mg, taken orally twice daily. The trial enrolled single patient dose escalation cohorts in an accelerated titration design. Trial objectives include evaluation of safety, tolerability, pharmacodynamics (PD), pharmacokinetics (PK) and tumor response evaluated using RECIST v1.1 criteria.

As of the data cut-off date of October 11, 2019, 12 patients across all dose levels were evaluable for response with at least one radiographic scan.

At the highest dose (600 mg BID), three of five (3/5) evaluable patients with NSCLC and one of two (1/2) evaluable patients with CRC achieved a partial response (PR); the remaining patients experienced stable disease (SD).

Across all dose levels, three of six (3/6) patients with NSCLC and one of four (1/4) patients with CRC achieved a PR. Two responding patients (1 NSCLC and 1 CRC) achieved confirmed PRs, both with continuing tumor shrinkage following their first scan. The other two patients with PRs (both NSCLC) remain on study but have not yet had confirmatory scans.

Clinical PK data demonstrated that the dose of 600 mg BID results in drug levels that meet or exceed those likely to lead to full inhibition of KRAS G12C signaling.

Treatment duration across all dose levels ranged from 6.7- 38.6 weeks for patients with NSCLC and 9.9-30.1 weeks for patients with CRC as of the data cut-off.

Treatment-related adverse events (AEs) were primarily grade 1 events. One patient experienced a dose-limiting toxicity (DLT) at the 1200 mg QD dose (capsule burden intolerance [12 capsules]) and one patient experienced a DLT at the 600 mg BID dose (grade 3/4 isolated amylase/lipase increase). The MTD has not yet been established and further dose escalation may be explored. Enrollment into dose expansion at the 600 mg BID dose is underway.

"There are currently no effective targeted therapies for patients with KRAS-mutant cancers," said Pasi A. Jänne, M.D., Ph.D., Director of The Lowe Center for Thoracic Oncology at the Dana Farber Cancer Institute and MRTX849-001 investigator. "KRAS mutations are the most common oncogenic alteration in all of human cancers, and as such, finding a therapeutic approach for this subset of cancers would have tremendous clinical impact for cancer patients."

In addition, data demonstrating the efficacy of MRTX849 in preclinical studies were published simultaneously with the oral presentations at 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 Cancer Discovery, a journal of the American Association of Cancer Researchers (AACR) (Free AACR Whitepaper). "The KRAS G12C Inhibitor, MRTX849, Provides Insight Toward Therapeutic Susceptibility of KRAS Mutant Cancers in Mouse Models and Patients," by lead author Jill Hallin, Principal Scientist at Mirati and corresponding author James G. Christensen, Ph.D. Executive Vice President and Chief Scientific Officer at Mirati, describes the challenging research path leading to a novel therapy that directly targets KRAS. Cancer Discovery publishes high-impact, peer-reviewed articles describing major advances in research and clinical trials.

About MRTX849

MRTX849 is an investigational, orally-available small molecule that is designed to potently and selectively inhibit a form of KRAS which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of NSCLC adenocarcinoma patients, 4% of colorectal cancer patients, and subsets of other types of cancer. Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. MRTX849 is being evaluated in a Phase 1/2 trial treating patients with molecularly-identified, KRAS G12C-positive advanced solid tumors.

APX3330 Phase I oncology trial presented at AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Meeting

On October 28, 2019 Apexian Pharmaceuticals, Inc., a clinical stage drug development company focused on advancing APX3330 for the treatment of diseases mediated by the APE1/Ref-1 protein, reported additional data on their Phase 1 study using APX3330 in patients with advanced solid tumors (Press release, Apexian Pharmaceuticals, OCT 28, 2019, View Source [SID1234549919]). Results of the trial were presented as a talk in the "Spotlight on Proffered Papers: Emerging Data from Phase I Trials of New Molecular Entities" session on Sunday, October 27.

An additional presentation followed in a poster session. The presentations occurred at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)-National Cancer Institute-European Organization for Research and Treatment of Cancer (AACR-NCI-EORTC) (Free AACR-NCI-EORTC Whitepaper) annual international meeting in Boston, MA. The presentation titled "A phase I study targeting the APE1/Ref-1 DNA repair-redox signaling protein with the APX3330 inhibitor" was presented by Dr. Mark R. Kelley, Chief Scientific Officer of Apexian and Professor of Pediatrics, Indiana University Simon Cancer Center.

"As we continue development of APX3330 for cancer and other indications, we are very pleased to have been selected to present our phase I trial findings in a platform talk and poster presentation" said Dr. Mark Kelley, Chief Scientific Officer of Apexian. "APX3330 is an oral drug and we observed a strong safety profile, recommended phase 2 dose, predicted PK and target engagement of APX3330 on APE1/Ref-1 using transcriptome and proteomic analysis of tumors".

Dr. Richard Messmann, Chief Medical Officer of Apexian added, "The APE1/Ref-1 protein plays a critical role in mediating a variety of diseases. Our phase I data have now confirmed that APX3330 targets the APE1 protein as expected. These findings pave the way toward confirming the utility of APX3330 in treating diseases as diverse as cancer, diabetic retinopathy, and inflammatory bowel disease, all mediated by the APE1/Ref-1 protein."

Zymeworks Announces Phase 1 Data for ZW25 in Combination with Chemotherapy in Advanced Gastroesophageal Adenocarcinoma at AACR-NCI-EORTC International Conference

On October 28, 2019 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional therapeutics, reported the first data from its Phase 1 study evaluating novel bispecific antibody ZW25 in combination with chemotherapy in HER2-expressing gastroesophageal adenocarcinoma (GEA) in a poster presentation 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), taking place October 26 – 30 in Boston (Press release, Zymeworks, OCT 28, 2019, View Source [SID1234549918]).

"Today we report the promising anti-tumor activity of ZW25 in combination with chemotherapy for people with HER2-expressing GEA," said Diana Hausman, M.D., Chief Medical Officer at Zymeworks. "These results compare favorably with current standard of care treatments for patients who have progressed after first-line therapies, including trastuzumab and chemotherapy. The data further support the prioritization of our ongoing Phase 2 trial of ZW25 plus chemotherapy as a first-line treatment for GEA and our goal of establishing ZW25 as the new best-in-class therapy for people with HER2-expressing cancers."

The FDA has granted Fast Track designation to ZW25 for first-line HER2-positive GEA in combination with standard of care chemotherapy, and a Phase 2 trial evaluating combination treatment in this setting is actively enrolling patients (NCT03929666).

"The patients in this Phase 1 study have a difficult-to-treat, advanced stage of cancer, which has progressed despite multiple prior therapies," said Funda Meric-Bernstam, M.D., Professor and Chair of the Department of Investigational Cancer Therapeutics, Medical Director of the Institute for Personalized Cancer Therapy at The University of Texas MD Anderson Cancer Center. "The preliminary activity and tolerability of ZW25 combination treatment with paclitaxel or capecitabine brings hope to these patients and warrants further investigation in a first-line setting."

Clinical Data Presented Today

Safety and Efficacy of ZW25, a HER2-Targeted Bispecific Antibody in Combination with Chemotherapy in Patients with Locally Advanced and/or Metastatic HER2-Expressing Gastroesophageal Cancer (Abstract# B001, Poster Presentation on Monday, October 28 at 12:30 pm ET)

The results from part three of an ongoing Phase 1 study present the safety and efficacy of ZW25, at the recommended dose of 20 mg/kg every other week, in combination with paclitaxel or capecitabine as a treatment for 14 patients with heavily pretreated HER2-expressing GEA. Patients received a median of 2.5 prior systemic therapies, and 93% had progressed following trastuzumab treatment.

Nine of 14 patients were response-evaluable. Overall, the majority of patients experienced a decrease in their target lesions with a disease control rate of 78%, comprising five (56%) partial responses and two (22%) stable disease. These responses were observed in both low and high HER2-expressing GEA. At the time of the data cut-off, four of the five partial responses had been confirmed, and five (56%) response-evaluable patients were still on study.

The overall safety profile of ZW25 plus chemotherapy was similar to that seen with chemotherapy alone. The most common treatment-related adverse events (TRAE) occurring in two or more patients were primarily Grade 1 or 2 and manageable with symptomatic treatment. Of the TRAE occurring in two or more patients, Grade 3 or higher events attributed to ZW25 and/or chemotherapy were fatigue and neutropenia (2 patients each) and stomatitis, peripheral neuropathy, and hypokalaemia (1 patient each). Five patients had chemotherapy dose reductions due to TRAEs, but no patients needed ZW25 dose reductions due to adverse events.

About the Phase 1 Clinical Trial

Zymeworks’ Phase 1 study has three parts. From part one of the study (the dose-escalation phase), the recommended single-agent dose was determined to be 20 mg/kg once every two weeks or 10 mg/kg weekly. In the second part of the study (the cohort expansion phase), additional patients are being enrolled to further assess ZW25’s single-agent tolerability and anti-tumor activity against a variety of cancer types in different settings. The third part of the study (the combination phase) is underway and evaluating ZW25 in combination with selected chemotherapy agents in patients with HER2 high or lower HER2 expression levels.

About ZW25

ZW25 is being evaluated in Phase 1 and Phase 2 clinical trials across North America and South Korea. It is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two distinct locations on HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging anti-tumor activity in patients. Zymeworks is developing ZW25 as a HER2-targeted treatment option for patients with any solid tumor that expresses HER2. The FDA has granted Fast Track designation to ZW25 for first-line gastroesophageal adenocarcinoma in combination with standard of care chemotherapy and Orphan Drug designation to ZW25 for the treatment of both gastric and ovarian cancers.