On December 11, 2018 Tocagen Inc. (Nasdaq: TOCA), a clinical-stage, cancer-selective gene therapy company, reported that it has commenced an underwritten public offering of 3,000,000 shares of its common stock (Press release, Tocagen, DEC 11, 2018, View Source [SID1234532011]). All shares of common stock to be sold in the offering will be offered by Tocagen. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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Citigroup and Leerink Partners are acting as joint book-running managers for the offering. Tocagen expects to grant the underwriters of the offering a 30-day option to purchase up to an additional 450,000 shares of its common stock at the public offering price, less the underwriting discounts and commissions.

The securities described above are being offered by Tocagen pursuant to a shelf registration statement on Form S-3 filed by Tocagen with the Securities and Exchange Commission (SEC), which was declared effective on May 23, 2018. A preliminary prospectus supplement and accompanying prospectus related to the offering will be filed with the SEC and will be available for free on the SEC’s website at View Source Copies of the preliminary prospectus supplement and the accompanying prospectus related to this offering, when available, may be obtained from: Citigroup Global Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (800) 831-9146; or Leerink Partners LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, or by telephone at (800) 808-7525, ext. 6132, or by e-mail at [email protected].

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 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.

On December 11, 2018 Cellectar Biosciences, Inc. (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted treatments for cancer, reported that the Japan Patent Office has granted the patent titled "Phospholipid Analogs as Diapeutic Agents and Methods of Use Thereof" with application number 2016135920 (Press release, Cellectar Biosciences, DEC 11, 2018, View Source [SID1234532012]). The patent provides composition of matter and use protection for the company’s proprietary phospholipid ether (PLE) analogs and specifically CLR 131 in breast, brain, leukemias and a variety of other cancers.

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"Certain cancers such as pediatric lymphomas and leukemias have a higher prevalence in Asia and represent unmet need both within and outside the region," said Jim Caruso, president and chief executive officer of Cellectar Biosciences. "The issuance of this patent enhances our growing intellectual property portfolio in this strategically important market and provides incremental value to CLR 131 and our PLE delivery franchise."

About Phospholipid Drug Conjugates

Cellectar’s product candidates are built upon a patented delivery and retention platform that utilizes optimized phospholipid ether-drug conjugates (PDCs) to target cancer cells. The PDC platform selectively delivers diverse oncologic payloads to cancerous cells and cancer stem cells, including hematologic cancers and solid tumors. This selective delivery allows the payloads’ therapeutic window to be modified, which may maintain or enhance drug potency while reducing the number and severity of adverse events. This platform takes advantage of a metabolic pathway utilized by all tumor cell types in all cell cycle stages. Compared with other targeted delivery platforms, the PDC platform’s mechanism of entry does not rely upon specific cell surface epitopes or antigens. In addition, PDCs can be conjugated to molecules in numerous ways, thereby increasing the types of molecules selectively delivered. Cellectar believes the PDC platform holds potential for the discovery and development of the next generation of cancer-targeting agents.

About CLR 131

CLR 131 is Cellectar’s investigational radioiodinated PDC therapy that exploits the tumor-targeting properties of the company’s proprietary PLE and PLE analogs to selectively deliver radiation to malignant tumor cells, thus minimizing radiation exposure to normal tissues. CLR 131 is in a Phase 2 clinical study in relapsed/refractory multiple myeloma (R/R MM) and a range of B-cell malignancies, and a Phase 1b clinical study in patients with R/R MM exploring fractionated dosing. The objective of the multicenter, open-label, Phase 1b dose-escalation study is the characterization of safety and tolerability of CLR 131 in patients with R/R MM. Patients in Cohorts 1-4 received single doses of CLR 131 ranging from 12.5 mCi/m2 to 31.25 mCi/m2 as well as a fractionated dose of 15.625 mCi/m2 given twice over seven days in Cohort 5. All study doses and regimens have been deemed safe and well tolerated by an independent Data Monitoring Committee. The company plans to initiate a Phase 1 study with CLR 131 in pediatric solid tumors and lymphoma as well as a second Phase 1 study in combination with external beam radiation for head and neck cancer.

On December 11, 2018 Athenex, Inc., a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer, reported that its global Phase 1b clinical trial of Oraxol (oral paclitaxel plus HM30181A) plus ramucirumab (monoclonal antibody to VEGF-R2) in gastric cancer patients who failed previous chemotherapies has completed the study of the second cohort of patients (Press release, Athenex, DEC 11, 2018, View Source;p=RssLanding&cat=news&id=2380209 [SID1234532013]). The results indicated strong positive signals of efficacy and the treatment was well tolerated.

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In the first cohort of six patients treated with a 200 mg/kg dose of Oraxol, partial responses were observed in 2/6 patients (33.3%) and stable disease observed in 1/6 patient (16.7%). There was one severe adverse event (SAE) of grade-4 neutropenia in one patient who had complete recovery from this event.

Athenex now reports that for the second cohort of six patients on an escalated Oraxol dose of 250 mg/kg, partial response, according to RECIST criteria, occurred in 3 patients (50%). There was one SAE of grade-3 vomiting in one patient, who elected to withdraw from the study and subsequently had complete recovery. The Oraxol dose is currently being further escalated to 300 mg/kg in the third cohort of patients and the study is ongoing.

"We are pleased by the strong positive signals of efficacy together with a good safety profile in this Phase 1b clinical trial of Oraxol plus ramucirumab in the second-line treatment of gastric cancer patients so far and look forward to further results from the continuation of this study. The results also echoed the strong positive signal that we have observed in other clinical studies of Oraxol as monotherapy for the treatment of metastatic breast cancer," stated Dr. Rudolf Kwan, Athenex’s Chief Medical Officer.

Oraxol is a novel oral formulation of paclitaxel currently in Phase 3 clinical trial in metastatic breast cancer.

Ramucirumab, as a single agent or in combination with paclitaxel, is FDA-approved for the treatment of patients with advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy. Ramucirumab is manufactured and marketed by Eli Lilly and Company under the name CYRAMZA.

The Orascovery platform was initially developed by Hanmi Pharmaceuticals and licensed exclusively to Athenex for all major worldwide territories except Korea, which is retained by Hanmi.

PharmaEssentia Corp. licensed the Taiwan, Singapore and Vietnam rights of Oraxol from Athenex and is a partner in the development of Oraxol in the territory

On December 11, 2018 NexImmune, an emerging leader in the field of antigen-directed immunotherapy, reported that the United States Patent and Trademark Office has issued a new method of use patent to Johns Hopkins University related to the Company’s E+E (T cell Enrichment and Enhancement) technology for which NexImmune holds an exclusive license from Johns Hopkins (Press release, NexImmune, DEC 11, 2018, View Source [SID1234554955]). This further enhances the company’s AIM technology intellectual property portfolio and provides broad intellectual property rights protecting key aspects of the company’s lead product AIM ACT, an adoptive T cellular therapy for the treatment of cancer.

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"Using our proprietary E+E technology to generate antigen-specific T cells represents a uniquely differentiated approach to expanding polyclonal T cells that are highly antigen-specific, highly polyfunctional and with a phenotypic composition optimized for anti-tumor cytotoxicity, proliferative capacity and long-term immunologic memory. We believe our AIM E+E generated T cell products have the potential to address some of the clinical limitations observed with currently available genetically modified T cell therapies. Our hope is that these differences translate into meaningful benefit for patients suffering from a variety of hematological malignancies," commented Scott Carmer, Chief Executive Officer of NexImmune. "Ensuring a robust intellectual property position around E+E is inherent to advancing the program and the claims granted in this patent exemplify the novel science behind this exciting technology."

U.S. patent 10,098,939 adds to previously issued U.S. and international counterpart patents and patent applications that form NexImmune’s AIM patent portfolio. Claims were granted on the ability of E+E to expand large numbers of antigen-specific T cells from the body’s endogenous T cell repertoire. Preclinical studies have demonstrated that cells generated using E+E have a large proportion of highly functional central and effector memory T cells which the company believes will provide both a potent immediate therapeutic benefit for cancer patients and an enhanced durability of response compared to currently approved adoptive T cell therapies. NexImmune plans to advance its AIM ACT platform into early phase clinical trials in 2019.

On December 11, 2018 INmune Bio, Inc., an immunotherapy company developing treatments to reprogram the innate immune system, reported that its lead drug candidate for treatment-resistant cancers, INB03, successfully inhibited the proliferation of tumor growth in pre-clinical models of trastuzumab treatment-resistant breast cancer (Press release, INmune Bio, DEC 11, 2018, View Source [SID1234531998]). The study was conducted by Roxana Schillaci, PhD., Researcher at the Institute of Biology and Experimental Medicine (IBYME-CONICET). Dr. Schillaci presented the data during a poster presentation at the San Antonio Breast Cancer Symposium in San Antonio, Texas, on December 8th.

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In the United States, one out of eight women will develop invasive ductal carcinoma (IDC) breast cancer in their lifetime. Two of those eight will have human epidermal growth factor receptor 2 (HER2) positive breast cancer that is treated with trastuzumab, an immunotherapy targeting HER2. Primary or secondary treatment resistance is a significant clinical problem that occurs in up to half of patients receiving trastuzumab for treatment of their HER2 positive breast cancer.

"Today, the definition of trastuzumab resistant breast cancer is the progression of breast cancer while the patient is on trastuzumab therapy," said Dr. Schillaci. "Our work shows that mucin 4 (MUC4) proteins, that block trastuzumab from binding with HER2 receptors, can be used as a biomarker to predict treatment-resistance. Additionally, the data shows that trastuzumab resistance can be reversed by eliminating soluble tumor necrosis factor (sTNF) in the tumor microenvironment".

Dr. Schillaci’s work showed that expression of MUC4 protein on cancer cells predicts trastuzumab resistance. The expression of MUC4 is caused by sTNF. Dr. Schillaci used INB03 to inhibit sTNF in mice to decrease MUC4 expression and reverse trastuzumab resistance. In further work, Dr. Schillaci’s team demonstrated that women resistant to trastuzumab express MUC4 on tumor while patients sensitive to trastuzumab do not.

"The results of this study suggest a possible solution for an ongoing problem in the treatment of women with HER2 positive breast cancer – predicting and treating trastuzumab resistance", said RJ Tesi, M.D., CEO and Co-Founder of INmune Bio. "If this work is confirmed in the clinic, the addition of therapy targeting sTNF, such as INB03, may improve the treatment options for a group of women previously unable to benefit from immunotherapy with trastuzumab."

INmune Bio initiated a Phase I clinical trial of INB03 on May 23. The company’s other drug candidate, INKmune, will enter clinical trials in early 2019.