On February 3, 2020 Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, reported that the Japanese Patent Office has granted the patent titled "Novel Peptides and Analogs for Use in the Treatment of Oral Mucositis (Press release, Soligenix, FEB 3, 2020, View Source [SID1234553785])." This allowance builds on similar intellectual property in the United States (US), New Zealand, Australia and Singapore and patent applications pending in other jurisdictions worldwide. The new claims cover therapeutic use of dusquetide (active ingredient in SGX942) and related innate defense regulator (IDR) analogs, and add to composition of matter claims for dusquetide and related analogs that have been granted in the US and worldwide. Dusquetide previously demonstrated positive results in a Phase 2 oral mucositis clinical trial and a pivotal Phase 3 study is ongoing, with a positive interim analysis completed in August 2019 and final topline results expected in Q2 2020.

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Based on the positive and previously published Phase 2 results, the pivotal Phase 3 clinical trial is a highly powered, double-blind, randomized, placebo-controlled, multinational trial. The study, called DOM-INNATE (Dusquetide treatment in Oral Mucositis – by modulating INNATE immunity), is enrolling approximately 260 subjects with head and neck cancer (HNC) undergoing standard chemoradiation therapy (CRT) and who are therefore at high risk of developing severe oral mucositis. Enrollment is ongoing in the US and across Europe with enrollment completion expected in Q1 2020 and final topline primary endpoint results anticipated in Q2 2020.

"Soligenix continues to pursue broad patent coverage for its IDR technology, including dusquetide, first with composition of matter claims followed by therapeutic use claims in oral mucositis," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "Having successfully pursued composition of matter claims in jurisdictions worldwide, we continue to pursue therapeutic use claims like those issued in the US previously and in Japan with this most recent patent. The therapeutic use claims are expected to be generally valid until 2034, which provides significant patent protection and life to dusquetide and our other IDRs. This allowance is timely as we continue to have discussions with potential strategic partners and pursue all options to advance our pipeline and plan for commercial activities."

About Oral Mucositis

Mucositis is the clinical term for damage done to the mucosa by anticancer therapies. It can occur in any mucosal region, but is most commonly associated with the mouth, followed by the small intestine. It is estimated, based upon review of historic published studies and reports and an interpolation of data on the incidence of mucositis, that mucositis affects approximately 500,000 people in the US per year and occurs in 40% of patients receiving chemotherapy. Mucositis can be severely debilitating and can lead to infection, sepsis, the need for parenteral nutrition and narcotic analgesia. The gastrointestinal damage causes severe diarrhea. These symptoms can limit the doses and duration of cancer treatment, leading to sub-optimal treatment outcomes.

The mechanisms of mucositis have been extensively studied and have been recently linked to the interaction of chemotherapy and/or radiation therapy with the innate defense system. Bacterial infection of the ulcerative lesions is now regarded as a secondary consequence of dysregulated local inflammation triggered by therapy-induced cell death, rather than as the primary cause of the lesions.

It is estimated, based upon review of historic published studies and reports and an interpolation of data on the incidence of oral mucositis, that oral mucositis in HNC is a subpopulation of approximately 90,000 patients in the US, with a comparable number in Europe. Oral mucositis almost always occurs in patients with HNC treated with CRT and is severe, causing inability to eat and/or drink, in >80% of patients. It is common (40-100% incidence) in patients undergoing high dose chemotherapy and hematopoietic cell transplantation, where the incidence and severity of oral mucositis depends greatly on the nature of the conditioning regimen used for myeloablation.

In the pediatric population, head and neck cancer is a rarer occurrence and is caused by different underlying pathologies. The major types of HNC in children are lymphoma, sarcomas (including rhabdomyosarcomas), and neuroblastoma rather than squamous cell carcinoma, the major type of adult HNC cancers. Hematopoietic stem cell transplantation (HSCT), especially allogeneic transplantation with higher risk of oral mucositis, is more frequently used in the pediatric population than in adults when treating a number of primary tumor types, as seen in leukemia and lymphoma. Both treatment of HNC and HSCT are associated with high risk of oral mucositis in the pediatric population.

Oral mucositis remains an area of unmet medical need where there are currently no approved drug therapies in the context of any solid tissue tumors.

About Dusquetide

Dusquetide (the active ingredient in SGX942) is an IDR, a new class of short, synthetic peptides. It has a novel mechanism of action whereby it modulates the body’s reaction to both injury and infection towards an anti-inflammatory, anti-infective and tissue healing response. IDRs have no direct antibiotic activity but, by modulating the host’s innate immune system responses, increase survival after infections caused by a broad range of bacterial Gram-negative and Gram-positive pathogens. It also accelerates resolution of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma and chemo- and/or radiation therapy. Preclinical efficacy and safety has been demonstrated in numerous animal disease models including mucositis, colitis, macrophage activation syndrome (MAS) as well as bacterial infections, including melioidosis.

SGX942 has demonstrated safety and tolerability in a Phase 1 clinical study in 84 healthy human volunteers. Positive efficacy results were demonstrated in an exploratory Phase 2 clinical study (Study IDR-OM-01) in 111 patients with oral mucositis due to CRT for HNC, including potential long-term ancillary benefits. Soligenix is working with leading oncology centers in the US and Europe to advance SGX942 in oral mucositis with the conduct of a pivotal Phase 3 clinical trial (Study IDR-OM-02) referred to as the "DOM–INNATE" study (Dusquetide treatment in Oral Mucositis – by modulating INNATE immunity). The multinational, placebo-controlled, randomized Phase 3 study is targeted to enroll approximately 260 subjects with squamous cell carcinoma of the oral cavity and oropharynx, scheduled to receive a minimum total cumulative radiation dose of 55 Gy fractionated as 2.0-2.2 Gy per day with concomitant cisplatin chemotherapy given as a dose of 80-100 mg/m2 every third week. Subjects are randomized to receive either 1.5 mg/kg SGX942 or placebo given twice a week during and for two weeks following completion of CRT. The primary endpoint for the study is the median duration of severe oral mucositis, assessed by oral examination at each treatment visit and then through six weeks following completion of CRT. Oral mucositis is evaluated using the WHO (World Health Organization) Grading system. Severe oral mucositis is defined as a WHO Grade of ≥3. Subjects are to be followed for an additional 12 months after the completion of treatment. An interim analysis for this study has been completed and identified a promising signal.

SGX942 has received Fast Track Designation from the FDA for the treatment of oral mucositis as a result of radiation and/or chemotherapy treatment in HNC patients, as well as Promising Innovative Medicine designation in the United Kingdom by the Medicines and Healthcare Products Regulatory Agency for the treatment of severe oral mucositis in HNC patients receiving CRT. In addition, products containing the same active ingredient, dusquetide, have been granted Fast Track Designation as an adjunctive therapy with other antibacterial drugs, for the treatment of melioidosis and Orphan Drug Designations in the treatment of MAS and the treatment of acute radiation syndrome.

Soligenix has a strong intellectual property position in the IDR technology platform, including composition of matter for dusquetide and related analogs. Dusquetide was developed pursuant to discoveries made by Professors B. Brett Finlay, PhD and Robert Hancock, PhD of the University of British Columbia, Canada. Soligenix has received partial funding from NIH for its oral mucositis clinical studies. The Phase 2 study was supported with a Phase I SBIR grant (#R43DE024032) award, with the Phase 3 study being supported by a Phase II SBIR grant (#R44DE024032) award.

On February 3, 2020 CytomX Therapeutics, Inc. (NASDAQ: CTMX), a clinical-stage oncology-focused biopharmaceutical company pioneering a novel class of investigational antibody therapeutics based on its Probody therapeutic technology platform, reported the appointment of Alison L. Hannah, M.D., as senior vice president and chief medical officer (Press release, CytomX Therapeutics, FEB 3, 2020, View Source [SID1234553784]).

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"Alison brings to CytomX broad and deep experience in guiding clinical stage therapies to registration," said Amy Peterson, M.D., chief development officer of CytomX Therapeutics. "She will be a tremendous asset to our company given her extensive and successful track record in clinical drug development."

Dr. Hannah brings 30 years of experience in the development of investigational cancer therapies having most recently served as a consultant to nearly 30 pharmaceutical and biotechnology companies. In this capacity, Dr. Hannah has successfully filed over 40 regulatory applications for First-in-Human clinical testing and has played significant roles in the broad marketing approval of 8 therapeutics (talazoparib, enzalutamide, defibrotide, carfilzomib, sunitinib, toceranib, irinotecan and filgrastim) including extensive experience interacting with global health and regulatory authorities. Earlier in her career, Dr. Hannah held the role of Senior Medical Director at SUGEN, Inc. (acquired by Pharmacia & Upjohn, now Pfizer) where she had oversight of clinical development, clinical operations, and pharmacovigilance. At SUGEN, she specialized in the development of tyrosine kinase inhibitors, including sunitinib (SUTENT) for kidney cancer. Dr. Hannah began her career at Quintiles, a global contract research organization, where she specialized in overseeing early to registrational-stage oncology clinical trials. Dr. Hannah currently serves on the board of NeoGenomics, a publicly traded cancer diagnostic company. Dr. Hannah received her B.A in biochemistry and immunology from Harvard University and her M.D. from the University of Saint Andrews.

"CytomX’s Probody technology represents a truly innovative approach to cancer drug development," said Alison Hannah, M.D., chief medical officer of CytomX Therapeutics. "I am pleased to be joining at a time where the advancement to Phase 2 with both of our wholly owned assets, CX-072 and CX-2009, and continued progress within our partnered programs, marks our dedication to helping oncology patients with serious unmet needs."

On February 3, 2020 VBL Therapeutics (Nasdaq: VBLT), a clinical-stage biotechnology company focused on the discovery, development and commercialization of first-in-class treatments for cancer, reported that Prof. Dror Harats, M.D., Chief Executive Officer, will present a corporate overview at the BIO CEO & Investor Conference, being held at the Marriott Marquis Times Square on February 10-11, 2020, in New York City (Press release, VBL Therapeutics, FEB 3, 2020, View Source [SID1234553783]).

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Presentation Details:
Date: Monday, February 10th
Time: 10:15 AM Eastern Time
Location: Marriott Marquis Times Square
Presentation Room: Wilder (4th Floor)
Webcast: Webcast

On February 3, 2020 Kitov Pharma Ltd. ("Kitov") (NASDAQ/TASE: KTOV), a clinical-stage company advancing first-in-class therapies to overcome tumor immune evasion and drug resistance, reported receipt from the U.S. Patent and Trademark Office (USPTO) of a Notification of Issuance for a patent application entitled, "Humanized antibodies against CEACAM1 (Press release, Kitov Pharmaceuticals , FEB 3, 2020, View Source [SID1234553782])." The patent, which expires in 2035, covers protein and DNA sequences pertaining to humanized antibodies capable of specific binding to human CEACAM1 molecules, including Kitov’s first-in-class monoclonal antibody, CM-24, pharmaceutical compositions comprising these antibodies, as well as methods for their use in treating and diagnosing cancer and other conditions.

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"This recognition from the USPTO validates the unique profile of Kitov’s CM-24. The mechanism of action of CM-24 results in an enhanced cytotoxic activity of the immune system cells, inducing a tumor’s death," commented Isaac Israel, Chief Executive Officer of Kitov. "CEACAM1 expression was found to correlate with poor prognosis in patients with non-small cell lung cancer (NSCLC). We strongly believe that the combination of CM-24 with nivolumab has the potential to result in a significant synergistic benefit in patients with NSCLC tumors expressing CEACAM1. We look forward to the initiation of our phase 1/2 clinical trial with CM-24 in the second half of 2020."

About CM-24

CM-24 is a clinical-stage monoclonal antibody blocking CEACAM1, a well-validated target which is highly expressed in many solid tumors as well as on immune cells and plays a pivotal role in the immune system by blocking immune cells’ access to tumors by CEACAM1-CEACAM1 and CEACAM1-CEACAM5 interaction. CEACAM1 was also shown to regulate TIM3 which induce immune fatigue. This unique mechanism of action positions CM-24 with a differentiated inhibitor of a multi-role immune checkpoint. In a monotherapy phase 1 study, CM-24 demonstrated safety and efficacy with standard dose in about 30% of patients. Kitov will advance CM-24 as a combination therapy with anti-PD1 checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC). Kitov has entered into a clinical collaboration agreement with Bristol Myers Squibb Company (NYSE:BMY) for the planned Phase 1/2 clinical trials to evaluate the combination of CM-24 with the PD-1 inhibitor nivolumab (Opdivo).

On February 3, 2020 Integra LifeSciences Holdings Corporation (NASDAQ:IART) reported that it has amended and extended its credit facility and commenced a private offering of convertible senior notes (Press release, Integra LifeSciences, FEB 3, 2020, View Source [SID1234553780]).

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Amendment and Extension of Credit Facility

Integra reported that it has amended and extended its credit facility with a bank group led by Bank of America, N.A. The overall size of the credit facility is approximately $2.2 billion and consists of a revolving line of credit of $1.3 billion and an $877.5 million term loan. The maturity of the credit facility was extended to February 3, 2025.

"We are pleased to announce this two-year extension of our credit facility under favorable terms," said Carrie Anderson, chief financial officer, Integra. "With these new terms, we have strengthened our balance sheet and increased our flexibility to pursue our long-term revenue growth and profitability strategy. We appreciate the continued support and commitment from our lending group."

Borrowings from the credit facility will be used to cover fees and expenses incurred in connection with the credit facility, for general corporate purposes and other permitted uses.

Private Placement of Convertible Senior Notes

Integra reported that it has commenced a private offering, subject to market conditions, of $500,000,000 aggregate principal amount of convertible senior notes due 2025 (the "Notes"). Integra expects to grant the initial purchasers of the Notes a 13-day option to purchase up to an additional $75,000,000 aggregate principal amount of Notes.

The Notes will be senior, unsecured obligations of Integra, and interest will be payable semi-annually in arrears. The Notes will mature on August 15, 2025, unless earlier converted, repurchased or redeemed in accordance with the terms of the Notes. Prior to 5:00 p.m., New York City time, on the business day immediately preceding February 15, 2025, the Notes will be convertible at the option of holders of the Notes only upon satisfaction of certain conditions and during certain periods, and thereafter, at any time until 5:00 p.m., New York City time, on the second scheduled trading day immediately preceding the maturity date. Upon conversion, the Notes may be settled in shares of Integra’s common stock, cash or a combination of cash and shares of the common stock, at the election of Integra. Prior to February 20, 2023, the Notes will not be redeemable. On or after February 20, 2023, Integra may redeem for cash all or part of the Notes, at its option, if the last reported sale price of Integra’s common stock has been at least 130% of the conversion price then in effect for at least 20 trading days (whether or not consecutive) during any 30 consecutive trading day period (including the last trading day of such period) ending on, and including, the trading day immediately preceding the date on which Integra provides notice of redemption.

Holders of the Notes will have the right to require Integra to repurchase for cash all or a portion of their Notes at 100% of their principal amount, plus any accrued and unpaid interest, upon the occurrence of a fundamental change (as defined in the indenture relating to the Notes). Integra will also be required to increase the conversion rate for holders who convert their Notes in connection with certain fundamental changes occurring prior to the maturity date or following delivery by Integra of a notice of redemption.

The interest rate, conversion rate, offering price and other terms are to be determined upon pricing of the Notes.

In connection with the pricing of the offering of the Notes, Integra expects to enter into privately negotiated convertible note hedge transactions with dealers, which may include initial purchasers and/or their respective affiliates (the "option counterparties"). These transactions are expected generally to reduce potential dilution to Integra’s common stock upon conversion of the Notes. Integra also expects to enter into warrant transactions with the option counterparties. The warrant transactions could separately have a dilutive effect on Integra’s common stock if the market price of Integra’s common stock exceeds the strike price of the warrants.

In connection with establishing their initial hedge of the convertible note hedge and warrant transactions, the option counterparties expect to enter into various derivative transactions with respect to Integra’s common stock concurrently with or shortly after the pricing of the Notes. These activities could have the effect of increasing (or reducing the size of any decrease in) the market price of Integra’s common stock.

Integra intends to use:

A portion of the net proceeds from the offering of the Notes to pay the cost of the convertible note hedge transactions (after such cost is partially offset by the proceeds from the sale of the warrant transactions).

Up to $100 million of the net proceeds from the offering of the Notes to repurchase shares of Integra’s common stock, including from certain purchasers of Notes in privately negotiated transactions effected through one of the initial purchasers or an affiliate thereof as Integra’s agent concurrently with the closing of the offering of the Notes, and through an accelerated share repurchase transaction (the "ASR transaction") with a dealer, which may be one of the initial purchasers or an affiliate thereof (the "ASR counterparty"), following the pricing of the offering of the Notes.

The remainder of the net proceeds from the offering of the Notes for general corporate purposes, which may include repayment of a portion of the indebtedness under Integra’s senior credit facility.

If the initial purchasers exercise their option to purchase additional Notes, Integra may sell additional warrants and use the net proceeds from the sale of the additional Notes, together with the proceeds from the additional warrants, to enter into additional convertible note hedge transactions. In addition, if the initial purchasers exercise their option to purchase additional Notes, Integra may use the remainder of the net proceeds from the sale of the additional Notes and the additional warrants for general corporate purposes, which may include the repayment of a portion of the indebtedness under Integra’s senior credit facility.

The settlement of the share repurchases from certain purchasers of Notes in privately negotiated transactions is conditioned upon the closing of the offering of the Notes. Integra expects the purchase price per share of common stock repurchased from certain purchasers of Notes in privately negotiated transactions concurrently with the closing of the offering of the Notes to equal the closing price per share of Integra’s common stock on the date of the pricing of the offering of the Notes. The purchase price per share of the common stock repurchased through the ASR transaction will generally be equal to the average volume-weighted average price of Integra’s common stock during a period beginning after the ASR transaction becomes effective, less a discount. The exact number of shares repurchased pursuant to the ASR transaction will be determined based on such purchase price.

In connection with the ASR transaction, the ASR counterparty or its affiliate expects to purchase or sell Integra’s common stock in secondary market transactions during the term of the ASR transaction. These activities and Integra’s repurchases of its common stock may raise or maintain the market price of Integra’s common stock or the Notes above market levels that otherwise would have prevailed or prevent or retard a decline in such market price. In the case of transactions in Integra’s common stock effected concurrently with the offering of the Notes, these transactions could affect the market price of Integra’s common stock concurrently with, or shortly after, the pricing of the Notes, and could result in a higher effective conversion price for the Notes.

The Notes will be offered to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act"). The Notes and the shares of Integra’s common stock issuable upon conversion of the Notes, if any, are not being registered under the Securities Act of 1933, as amended, or any state securities laws, and may not be offered or sold in the United States except pursuant to an exemption from the registration requirements of the Securities Act and any applicable state securities laws.

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