On September 20, 2018 AIVITA Biomedical reported that it has dosed its first of 10 patients currently enrolled as part of its Phase 2 trial in patients with advanced ovarian cancer (Press release, AIVITA Biomedical, SEP 20, 2018, View Source [SID1234529879]). The trial is designed to investigate AIVITA Biomedical’s patient-specific cancer treatment consisting of autologous dendritic cells loaded with autologous antigens from the patient’s tumor-initiating cells.

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AIVITA is enrolling approximately 99 patients in the Company’s ROOT OF CANCER ovarian cancer trial to be randomized in a 2:1 ratio to receive either the Company’s patient-specific cancer treatment or a control agent consisting of autologous monocytes. The treatment will be administered in a series of injections along with standard care.

"We’re proud of the manufacturing team here at AIVITA who have made this important moment possible," said Dr. Bob Dillman, Chief Medical Officer at AIVITA. "The team has contributed manufacturing efficiencies which have greatly improved the success rate and speed of creating this treatment, allowing us to treat more patients more reliably. We’ve since randomized several additional patients in this trial and activity is accelerating as we sign on more hospitals and receive additional tumors."

Previously, this treatment was tested in two Phase 2 trials in patients with advanced melanoma and approved for Phase 3 testing. The first Phase 2 trial demonstrated a 54% 5-year survival rate compared to a 29% 5-year survival rate for an active control arm. The second randomized Phase 2 trial demonstrated similar results, with a significantly longer median survival compared to the control arm.

AIVITA’s ROOT OF CANCER technology is also the subject of an ongoing Phase 2 clinical trial treating glioblastoma in the USA. The Company is also currently applying for conditional approval to commercialize the treatment for melanoma in Japan and is considering Japanese strategic partners for this program.

About Ovarian Cancer

Ovarian cancer is the fifth most common cause of female cancer deaths, with an estimated 22,240 new diagnoses in 2018 and 14,070 deaths. The median age at diagnosis is 63, with a 5-year survival rate of less than 50% for all, and about 35% for the two thirds who have advanced disease (stage III or IV) at the time of initial diagnosis. Current standard of care includes surgical debulking and several courses of chemotherapy.

About ROOT OF CANCER

AIVITA’s treatment is a platform technology applicable to most solid tumor types and consists of autologous dendritic cells loaded with autologous tumor antigens from autologous self-renewing tumor-initiating cells.

The ovarian Phase 2 double-blind study will enroll approximately 99 patients who will be randomized in a 2:1 ratio to receive either the autologous dendritic cell vaccine 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.

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

On September 26, 2018 NANOBIOTIX (Euronext: NANO – ISIN: FR0011341205), a late clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported it will present an update on and data from its NBTXR3 development program at the International Conference on Immunotherapy Radiotherapy Combinations that will take place from September 20 to 22, 2018 in Paris, France (Press release, Nanobiotix, SEP 20, 2018, View Source [SID1234529669]).

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Follow-up of Phase I/II in advanced Head and Neck cancers in elderly and frail patients ineligible for cisplatin or
intolerant to cetuximab In the Phase I part of this trial, which is conducted to determinate the recommended dose, 18 patients have been injected with NBTXR3. Follow-up of patients that received highest doses of NBTXR3 (15% and 22% dose levels) shows that every patient alive at the 12-month cut-off date was still alive after 23 months or more. At 26 months, one of the patients treated at the 15% dose level had died.

These data suggest the potential of NBTXR3 to impact survival for this advanced cancer patient population.
Immuno biomarker study in randomized phase II/III soft tissue sarcoma clinical trial Immunohistochemistry analyses revealed that, compared to radiation therapy alone (29 patients), NBTXR3 activated by radiation therapy (23 patients) increased the density of CD8+ T cell lymphocyte, and decreased FOXP3+ (Treg) into the tumors, while macrophage number remained relatively constant. These data indicate that NBTXR3 activated by radiation therapy could modulate the antitumor immune response.

In vivo investigation of NBTXR3 mode of action inducing distant immune response on CT26 tumoral model
Depletion experiment of CD8+ T cells (NBTXR3+3x4Gy+anti-CD8) induces a partial loss of tumor growth control of
treated tumors, and a complete abolition of the abscopal effect (distal tumors). This result indicates that the abscopal effect was driven by CD8+ T cells. Interestingly, depletion of CD4+ T cells (NBTXR3+3x4Gy+anti-CD4) increases the efficacy of NBTXR3 + radiation therapy at both sites (treated and distal tumors). As anti-CD4 treatment lead to Treg depletion (known to have a protumoral role), Treg depletion might have improved NBTXR3 radiation therapy treatment. These observations continue to support the rationale for the use of NBTXR3 activated by radiation therapy to seek to transform tumors

On September 20, 2018 Molecular Templates, Inc. (Nasdaq: MTEM) ("Molecular"), a clinical-stage oncology company focused on the discovery and development of proprietary engineered toxin bodies (ETBs), which are differentiated, targeted, biologic therapeutics for cancer, reported the pricing of its underwritten public offering of 8,200,000 shares of its common stock at a public offering price of $5.50 per share (Press release, Molecular Templates, SEP 20, 2018, View Source [SID1234529615]). The gross proceeds to Molecular from the offering, before deducting the underwriting discounts and commissions and estimated offering expenses payable by Molecular, are expected to be $45.1 million. All of the shares of common stock to be sold in the offering are being sold by Molecular. In addition, Molecular has granted to the underwriters a 30-day option to purchase up to 1,230,000 additional shares of common stock.

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Molecular intends to use the net proceeds from the offering, together with its existing cash and cash equivalents, to fund: its ongoing Phase Ib and Phase II clinical studies and planned additional Phase II clinical studies for MT-3724 in DLBCL; its share of development expenses in its CD38 collaboration with Takeda; its programs targeting HER2 and PD-L1; further preclinical development and drug discovery activities in its other programs and for working capital and general corporate purposes. The offering is expected to close on or about September 25, 2018, subject to the satisfaction of customary closing conditions.

Cowen, Evercore ISI and UBS Investment Bank are acting as joint book-running managers for the offering. Laidlaw & Company (UK) Ltd. is acting as lead manager for the offering. Ladenburg Thalmann is acting as financial advisor to Molecular.

The shares are being offered by Molecular pursuant to a shelf registration statement on Form S-3 that was previously filed with the U.S. Securities and Exchange Commission (the "SEC") and declared effective by the SEC. A preliminary prospectus supplement relating to the offering was filed with the SEC and a final prospectus supplement relating to the offering will be filed with the SEC. When available, copies of the final prospectus supplement and the accompanying prospectus relating to the offering may be obtained from Cowen and Company, LLC, c/o Broadridge Financial Services, 1155 Long Island Avenue, Edgewood, NY 11717, Attention: Prospectus Department, or by telephone at (631) 274-2806; Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 36th Floor, New York, NY 10055, by telephone at 888-474-0200, or by email at [email protected] or UBS Securities LLC, Attention: Prospectus Department, 1285 Avenue of the Americas, New York, NY 10019, by telephone at 1-888-827-7275 or by emailing [email protected]. You may also obtain these documents free of charge by visiting the SEC’s website at www.sec.gov.

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 registration or qualification under the securities laws of any such state or other jurisdiction.

On September 20, 2018 Exicure, Inc. (OTCQB:XCUR), the pioneer in gene regulatory and immunotherapeutic drugs utilizing three-dimensional spherical nucleic acid (SNA) constructs, reported Phase 1 results for AST-008, an SNA consisting of toll-like receptor 9 (TLR9) agonists designed for immuno-oncology applications (Press release, Exicure, SEP 20, 2018, View Source;p=RssLanding&cat=news&id=2368198 [SID1234529613]).

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"Phase 1 results for AST-008 demonstrated our desired highly potent immune system activation without serious adverse events or dose limiting toxicity. We believe this molecule could lead to better combination therapies for patients with cancer and, to that end, we expect to initiate a Phase 1b/2 trial in patients before year end," said Dr. David Giljohann, Chief Executive Officer of Exicure. "These data support the potential of our SNA platform for immuno-oncology and set the stage for ongoing development of the SNA platform into indications well beyond cancer."

Exicure’s Phase 1 Trial Results

The Phase 1 trial of AST-008 was a single ascending subcutaneous dose trial comprised of 16 healthy volunteers. AST-008 was shown to be safe and tolerable in all subjects, with no serious adverse events and no dose limiting toxicity. AST-008 was well tolerated and all AST-008-related adverse events were of short duration, reversible and consistent with TLR9 activation.

In addition to the principle safety and tolerability endpoint, the trial screened for levels of select cytokines and markers of immune cell activation. AST-008 was shown to elicit high levels of certain cytokines as well as activate important effector cells of the immune system including T cells and natural killer cells, the main drivers of anti-tumor response.

For the four subjects receiving the trial’s top dose of about 20 µg/kg of AST-008, initial analyses suggest that the average fold-increase above baseline for these cytokines is approximately as follows: IFN-gamma: 3 fold; IL-6: 57 fold; IL-12: 2 fold; IP-10: 32 fold; and MCP-1: 4 fold. At this dose, AST-008 also elicited 9.5 fold and 3.5 fold increases in the fraction of activated T cells and natural killer cells, respectively, compared to baseline.

Exicure’s Planned Phase 1b/2 Patient Trial

Exicure intends to begin an open-label Phase 1b/2 trial of intra-tumorally dosed AST-008 in combination with a checkpoint inhibitor before year end. The trial will begin with an AST-008 dose finding Phase 1b stage, followed by a Phase 2 expansion stage. In the Phase 1b, Exicure will enroll patients with superficial injectable tumors and will prioritize those with Merkel cell carcinoma, cutaneous squamous cell carcinoma, melanoma, and squamous cell carcinoma of the head and neck. Preliminary data from the Phase 1b stage are expected in late 2019.

Historical TLR9 Agonist Healthy Volunteer Data

In 2015, Mologen AG published results (European Journal of Cancer, 2015, volume 51, supplement 1, page S12) from a healthy volunteer trial. In a single cohort, 13 subjects each received one 60 mg dose (equivalent to 923 µg/kg for a 65 kg subject) of lefitolimod subcutaneously. On average, across the cohort, there was a 7 fold-increase in IP-10 expression above baseline. No cell activation data were reported. Lefitolimod is currently in a Phase 3 clinical trial.

In 2004, Coley Pharmaceutical Group (now Pfizer, Inc.) published results (Journal of Immunotherapy, 2004, Volume 27, pages 460–471) from a single ascending dose healthy volunteer trial. In that trial, their TLR9 agonist, PF-03512676, was administered subcutaneously to six subjects per dose level. For the 20 µg/kg dose level, the average fold-increase above baseline for these cytokines is as follows: IFN-gamma: no change from baseline; IL-6: 8 fold; IL-12: no change from baseline; IP-10: 9 fold; and MCP-1: 3 fold.

Upcoming Presentations

Exicure management expects to be presenting and available for meetings at a number of fall investor conferences including:

October 2 – Ladenburg Thalmann 2018 Healthcare Conference at the Sofitel Hotel New York, NY;
October 3 – Leerink Partners Roundtable Series: Rare Disease & Oncology at the Lotte New York Palace, New York, NY;
October 9 – Chardan’s 2nd Annual Genetic Medicines Conference at the Westin Grand Central, New York, NY;
October 25 – BTIG Biotech Conference at the Langham Hotel, New York, NY.

On september 20, 2018 RedHill Biopharma Ltd. (Nasdaq: RDHL) (Tel-Aviv Stock Exchange: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company primarily focused on proprietary drugs for gastrointestinal diseases, reported that Mr. Dror Ben-Asher, chief executive officer of RedHill, will present a corporate overview at the Ladenburg Thalmann 2018 Healthcare Conference, on Tuesday, Oct. 2, 2018, at 10:30 a.m. ET, at the Sofitel Hotel in New York City (Press release, RedHill Biopharma, SEP 20, 2018, View Source [SID1234529589]).

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The presentation will be broadcast live and available for replay on the Company’s website, View Source, for 30 days. Please access the website at least 15 minutes ahead of the presentation to register, download, and install any necessary audio software.