On August 15, 2018 CEL-SCI Corporation (NYSE American: CVM) reported that the Independent Data Monitoring Committee (IDMC) for the Company’s pivotal Phase 3 head and neck cancer study of its investigational immunotherapy Multikine* (Leukocyte Interleukin, Injection) has completed its recent review of the Phase 3 study data (Press release, Cel-Sci, AUG 15, 2018, View Source [SID1234528894]). The data from all 928 enrolled patients were provided to the IDMC by the clinical research organization (CRO) responsible for data management of this Phase 3 study.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The IDMC made the following recommendation:

The IDMC recommendation is to continue the trial until the appropriate number of events have occurred.
IDMCs are committees commonly used by sponsors of clinical trials to protect the interests of the patients and the integrity of the study data in ongoing trials, especially when the trials involve patients with life threatening diseases, and when, as in cancer clinical trials, they extend over long periods of time.

On August 15, 2018 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology (I-O) company with a pipeline of immune checkpoint antibodies, cancer vaccines and adoptive cell therapies1, reported that Merck, known as MSD outside the United States and Canada, initiated a Phase I clinical trial of an undisclosed antibody candidate discovered by Agenus, under the two companies license and research collaboration (Press release, Agenus, AUG 15, 2018, View Source [SID1234528898]). Based on this milestone and under the terms of the agreement, Agenus received a $4 million milestone payment and is entitled to receive up to an additional $95 million in success milestones from Merck.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We continue to deliver on all milestones with our existing partners." said Garo H. Armen, Ph.D., Chairman and CEO of Agenus. "This is yet another validation of our antibody discovery platform and expertise in the field and adds to our successes in delivering first in class discoveries to patients. Notably, besides this, we also have two other partnered programs advancing to the clinic this year, each triggering additional milestone payments to Agenus."

This milestone is the second under the collaboration, originally announced in April 2014. According to the terms of the agreement, Merck is responsible for all product development expenses for the antibody candidate, and Agenus is eligible to receive up to an additional $95 million in milestone payments, as well as royalties on worldwide product sales.

On August 15, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported a favorable review of safety data from the second dose cohort of patients who received one billion transduced SPEAR T‑cells targeting MAGE-A4 in the ongoing basket study in nine solid tumor indications (Press release, Adaptimmune, AUG 15, 2018, View Source;p=RssLanding&cat=news&id=2363723 [SID1234528864]). Based on these data, the Safety Review Committee (SRC) has endorsed dose escalation to the third dose cohort of 1.2 to 6 billion cells.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

To date, three patients have received 100 million transduced MAGE‑A4 SPEAR T-cells in the first dose cohort, and three patients received one billion cells in the second cohort. No evidence of toxicity related to off-target binding or alloreactivity has been reported. Most adverse events were consistent with those typically experienced by cancer patients undergoing cytotoxic chemotherapy or other cancer immunotherapies.

"In Cohorts 1 and 2, we have observed cell expansion consistent with the doses administered. We are initiating dosing with 1.2 to 6 billion cells in the MAGE-A10 and MAGE-A4 studies. We have a number of patients whose cell products have been manufactured and these cells can be used when patients are ready for therapy. We remain on track to deliver initial data on response assessments from these cohorts during the second half of 2018," said Rafael Amado, Adaptimmune’s President of Research & Development.

Overview of Study Design MAGE-A4 Pilot Study

This is a first-in-human, open-label study utilizing a modified 3+3 design in up to 36 patients with escalating doses of 100 million (Cohort 1), 1 billion (Cohort 2), and 1.2‑6 billion (Cohort 3) transduced SPEAR T-cells to evaluate safety, including dose limiting toxicities (DLTs) followed by a possible expansion phase with doses of up to 10 billion SPEAR T-cells
This active trial is being evaluated across nine solid tumor indications including urothelial, melanoma, head and neck, ovarian, NSCLC, esophageal, and gastric cancers; as well as synovial sarcoma and myxoid/round cell liposarcoma (MRCLS)
Patients are screened under a separate protocol (Screening Protocol: NCT02636855) to identify those who have the relevant HLA-A*02 alleles and MAGE-A4 tumor expression
There was a 21-day stagger between patients in Cohort 1, with this stagger dropping to 7 days in Cohorts 2, and 3. There is no pre-determined stagger in the potential expansion phase
Cohorts 1-3 were intended to enroll 3 patients each with an expansion to 6 patients if DLTs were observed
The expansion phase can enroll up to 30 patients
The lymphodepletion regimen are:
Cohorts 1 and 2 – fludarabine (flu) (30mg/m2/day) and cyclophosphamide (cy) (600 mg/m2/day) for 3 days
Cohorts 3 and expansion phase – flu (30mg/m2/day) for 4 days and cy (600 mg/m2/day) for 3 days
Efficacy is assessed by overall response rate, time to response, duration of response, progression-free survival, and overall survival at weeks 4, 8, and 12, month 6, and then every 3 months until confirmation of disease progression
Adaptimmune’s Pipeline
Adaptimmune’s proprietary technology enables the Company to consistently generate affinity enhanced T-cell receptors (TCRs) that address intracellular targets on solid tumors that may not be accessible to certain other immunotherapy treatment modalities. Adaptimmune has three wholly owned SPEAR T‑cells in active clinical trials, with additional first and next generation SPEAR T‑cells being evaluated by means of Adaptimmune’s proprietary preclinical testing platform in advance of proceeding to the clinic.

Adaptimmune’s wholly owned SPEAR T-cells targeting MAGE‑A10, MAGE‑A4, and AFP are being evaluated in four active clinical trials across ten solid tumor indications:

MAGE-A10: Two active trials, one in NSCLC, and a triple tumor study in urothelial (bladder), melanoma, and head & neck cancers
MAGE-A4: One active trial across nine solid tumor indications including urothelial, melanoma, head and neck, ovarian, NSCLC, esophageal, and gastric cancers; as well as synovial sarcoma and myxoid/round cell liposarcoma (MRCLS)
AFP: One active study in hepatocellular (liver) cancer
Patients are receiving doses of 1.2-6 billion SPEAR T-cells across all the MAGE-A4 and MAGE‑A10 trials as there has been no evidence of off-target toxicity, to date, which has supported dose escalation

On August 15, 2018 Delcath Systems, Inc. (OTCQB: DCTH), an interventional oncology company focused on the treatment of primary and metastatic liver cancers, reported its financial results for the quarter ended June 30, 2018 (Press release, Delcath Systems, AUG 15, 2018, View Source;p=RssLanding&cat=news&id=2363736 [SID1234528978]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Highlights from the second quarter of 2018 and recent weeks include:

Amendment of the Company’s ongoing Phase 3 clinical trial in ocular melanoma liver metastases to a non-randomized, single-arm trial
Initiation of a $50 million rights offering
Revenue from European sales for the quarter of approximately $0.9 million;
100th CHEMOSAT treatment performed at Leiden University Medical Center;
Inclusion of CHEMOSAT in the German national treatment guidelines for liver metastases from melanoma.
Announcement that the independent Data Safety Monitoring Board (DSMB) of the Phase 3 FOCUS clinical trial has again recommended that the study continue without modification;
Initiation of the ALIGN registration trial for the treatment of Intrahepatic Cholangiocarcinoma (ICC);
CHEMOSAT featured in main stage training presentation at European Conference on Interventional Oncology;
Management Commentary

"During our second quarter we continued to advance the major elements of our Clinical Development Program while taking steps to resolve the cash constraints and other restrictions that have impeded our ability to operate in recent weeks," said Jennifer K. Simpson, Ph.D., MSN, CRNP President and CEO of Delcath. "These efforts culminated with the announcements we made in July of the protocol amendment to our ongoing FOCUS Phase 3 trial in ocular melanoma liver metastases to permit a non-randomized single-arm study, and our $50 million rights offering. These are highly significant developments for Delcath, and together provide both a path toward an application for FDA approval and the necessary financing to achieve it."

"Revenues for the second quarter of 2018 were approximately $0.9 million, an increase of nearly 50% over approximately $0.6 million in the prior year quarter. During the quarter, we announced CHEMOSAT was included in the German national treatment guidelines for ocular melanoma liver metastases, and that our third European commercial treatment center achieved the 100-treatment milestone. To date centers in Europe have completed over 600 CHEMOSAT treatments. CHEMOSAT was also featured in a main state presentation at the ECIO annual meeting, demonstrating the continued interest in the European research community in PHP therapy’s potential.

"Regarding our FOCUS Phase 3 Trial, in addition to the protocol amendment we announced in May that the independent Data Safety Monitoring Board (DSMB) has completed another review of safety data for treated patients in the trial and again recommended that the study continue without safety related modification. Safety data for the amended trial will be pooled with all patients treated with Melphalan/HDS under the prior protocol.

"During the second quarter, we announced the initiation of our registration trial of Melphalan Hydrochloride for Injection for use with the Delcath Hepatic Delivery System (Melphalan/HDS) to treat patients with intrahepatic cholangiocarcinoma (ICC). Called The ALIGN Trial, this trial will seek to enroll approximately 295 ICC patients at approximately 40 clinical sites in the U.S. and Europe. The trial is being conducted under a Special Protocol Assessment (SPA) agreement reached with the U.S. Food and Drug Administration (FDA) in March 2017. The ALIGN Trial is based on a strong efficacy signal observed in the ICC tumor type through our commercial experience with CHEMOSAT in Europe. We are leveraging our existing network of trial sites from our FOCUS Phase 3 trial to rollout the trial protocol as efficiently as possible and have 3 centers open for patient enrollment to date. In this orphan population where there exists a huge unmet need, this trial provides us with a second pathway to commercial drug approval in the United States, and if successful we believe will be an important value driver for the Company.

"Though the recent months have been difficult we have taken significant steps to reduce our time to NDA submission, advance our clinical and commercial programs, and obtain the financial resources required to realize PHP therapy’s potential and return value to our shareholders," concluded Dr. Simpson.

Second Quarter 2018 Financial Results

Revenue for the three months ended June 30, 2018 was $0.9 million, up from $0.6 million for the prior year period driven by the establishment of reimbursement coverage of CHEMOSAT procedures in Germany. Selling, general and administrative expenses were approximately $2.6 million compared to $2.5 million in the prior year quarter, a slight increase related to decreased production and adjustments to overhead allocations. Research and development expenses for the current quarter increased to $4.1 million from $2.5 million in the prior year quarter, driven by increased costs associated primarily due to the ongoing accrual of the Company’s Phase 3 FOCUS trial. Total operating expenses for the current quarter were $6.7 million compared with $5.1 million in the prior year quarter.

The Company recorded net loss for the three months ended June 30, 2018, of $6.7 million, an increase of $4.7 million, or 242.6%, compared to a net loss of $1.9 million for the same period in 2017. This increase in net loss is primarily due to a $6.7 million decrease in interest expense primarily related to the amortization of debt discounts related to convertible notes that were fully satisfied in 2017, and a $2.6 million increase in the change in the fair value of the warrant liability, both non-cash items. Additionally, there was a $1.7 million increase in operating expenses primarily related to increased investment in our clinical trial initiatives.

Balance Sheet Highlights
At June 30, 2018, the Company had cash and cash equivalents totaling $1.3 million, as compared to cash and cash equivalents totaling $4.0 million at December 31, 2017 and $1.8 million at June 30, 2017. During the six months ended June 30, 2018 and June 30, 2017, the Company used $9.3 million and $8.1 million respectively, of cash in its operating activities. The Company believes that its capital resources are adequate to fund its operating activities through August 2018.

On June 4, 2018, the Company entered into a Securities Purchase Agreement (the "SPA") with an institutional investor pursuant to which the Company issued $3.3 million in principal face amount of senior secured convertible notes of the Company (the "Notes") and related Series D Warrants (the "Series D Warrants") to purchase additional shares of the Company’s common stock ("Common Stock"). $3.3 million of the Notes were issued for cash proceeds of $2.4 million with an original issue discount in the amount of $1.1 million.

On July 20, 2018, the Company entered into a Securities Purchase Agreement with another institutional investor for the remaining Notes and Warrants in proportionate amounts to those issued in the June 4, 2018 transaction which is discussed in Note 7, in a transaction exempt from registration pursuant to Section 4(a)(2) of the Securities Act and Rule 506(b) promulgated thereunder, and received gross proceeds of $1,600,000.

Rights Offering & Bridge Financing

On July 16, 2018 the Company filed a registration statement on Form S-1 with the SEC for a rights offering for up to 28,571,429 shares of common stock at the subscription price of $1.75 per share. The subscription period this rights offering began on Tuesday, August 7, 2018 upon declaration of effectiveness of its registration statement on Form S-1 by the SEC.

On August 15, 2018 RXi Pharmaceuticals Corporation (NASDAQ: RXII) a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (sd-rxRNA) therapeutic platform reported that it has entered into a research collaboration with the Karolinska Institutet in Stockholm, Sweden (Press release, RXi Pharmaceuticals, AUG 15, 2018, View Source [SID1234528886]). This collaboration will explore RXi’s sd-rxRNA compounds against targets involved in T cell and NK cell differentiation and/or in the immune cell tumor-induced stress response with the aim of producing anti-tumor adoptive cell therapy grafts with improved functionality and persistence.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This work will expand on the recently published results from the Kiessling group demonstrating that an sd-rxRNA targeting PD-1 can enhance TIL antitumor activity against melanoma cells in vitro, further showing that ex vivo treatment with the sd-rxRNA compounds was easily incorporated into a clinically relevant rapid expansion protocol for TILs.1

Dr. Gerrit Dispersyn, Chief Development Officer of RXi Pharmaceuticals, stated: "We are pleased to expand our collaboration with Dr. Kiessling’s group, to further harness their expertise in oncology and to expand on the successful research they have previously done with our sd-rxRNA technology platform in immuno-oncology. The combination of their prior results and the anticipated research results from this new collaboration are critical elements for a rapid advancement of sd-rxRNA immuno-oncology therapeutics into the clinic, further supported by our prior clinical experience with sd-rxRNA in other indications."

Rolf Kiessling, MD, PhD, Senior Professor in Experimental Oncology at the Karolinska Institutet, Senior Chief Physician at the Oncology clinic at the Karolinska University Hospital and member of RXi’s Scientific Advisory Board stated: "Our results to date provide direct clinical relevance for the use of sd-rxRNA technology to improve ACT. In this collaboration, we look forward to exploring using sd-rxRNA to modulate targets outside of checkpoints to improve efficacy of immune effector cells such as T cells and NK cells."

Immunotherapy of cancer has become increasingly important in clinical practice over the recent decade. By activating the patient’s immune system, immunotherapy treatments have shown remarkable promise in extending the lifespan of previously untreatable cancer patients. Adoptive cell therapy is an emerging immunotherapy approach which uses immune cells, such as T-lymphocytes or NK cells that are isolated from the patient or retrieved from allogeneic immune cell banks, and then expanded and in some cases processed to express tumor-binding receptors.

A new and important step in this ex-vivo processing of the immune cells is in development where self-delivering RNAi compounds (sd-rxRNA) are used to eliminate the expression of immunosuppressive receptors or proteins from the therapeutic immune cells, thereby making them less sensitive to tumor resistance mechanisms and improving their ability to destroy tumor cells. In this way, sd-rxRNA therapeutic compounds can be used to weaponize therapeutic immune cells to attack cancer and ultimately provide patients battling terminal cancers with a powerful new treatment option that goes beyond current treatment modalities.

About RXi Pharmaceuticals

RXi Pharmaceuticals Corporation (NASDAQ: RXII) is a biotechnology company developing the next generation of immuno-oncology therapeutics based on its self-delivering RNAi (sd-rxRNA) therapeutic platform. The Company’s discovery and research efforts are focused on developing sd-rxRNA therapeutic compounds to be used with an Adoptive Cell Transfer (ACT) approach. This process uses immune cells, such as T-lymphocytes that are isolated from the patient or retrieved from allogeneic immune cell banks, and then expanded and in some cases processed to express tumor-binding receptors. Our approach introduces a new and important step in ex-vivo processing of the immune cells where sd-rxRNA is used to eliminate the expression of immunosuppressive receptors or proteins from the therapeutic immune cells, making them less sensitive to tumor resistance mechanisms and thus improving their ability to destroy the tumor cells. Essentially, we aim to maximize the power of our sd-rxRNA therapeutic compounds by weaponizing therapeutic immune effector cells to attack cancer and ultimately provide patients battling terminal cancers with a powerful new treatment option that goes beyond current treatment modalities.