On December 11, 2017 RXi Pharmaceuticals Corporation (NASDAQ: RXII) reported that it has entered into a research collaboration with Medigene AG (MDG1, Frankfurt, Prime Standard, TecDAX) to explore potential synergies of using RXi’s self-delivering RNAi technology (sd-rxRNA) in combination with Medigene’s recombinant TCRs to develop modified T cells with enhanced efficacy and/or safety (Press release, RXi Pharmaceuticals, DEC 11, 2017, View Source [SID1234522533]). The preclinical research program will examine the applicability of RXi’s sd-rxRNA technology to be integrated into Medigene’s process to produce receptor-modified T cells with the ultimate goal to further improve Medigene’s T cell therapies for the treatment of cancer patients.

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Research teams at Medigene will closely work together with the scientists at RXi to explore potential advantages of transient down regulation of certain genes ("knock down") to prevent negative regulation of T cells expressing a recombinant TCR directed against a predefined tumor antigen. The two complementing technologies could lead to synergistic effects that might further sharpen and improve the therapeutic effects of Medigene’s receptor-modified T cells.

Markus Dangl, Senior Vice President Research and Preclinical Development of Medigene AG, comments: "We are very happy that we found a partner that is fully aligned with our vision to further improve our adoptive T cell therapy approach. We are convinced that this technology can help us to develop the next generation of recombinant T cells that are highly efficacious, also in challenging solid tumor environments. These T cells will contain features that have the potential to further enhance the efficacy and safety of our approach to bring highly beneficial cellular therapies to the market."

Dr. Geert Cauwenbergh, President and CEO of RXi Pharmaceuticals, adds: "We are excited to start this new collaboration. Medigene’s adoptive cell therapy, using their TCR platform, is a very attractive and promising development in immuno-oncology; and we are pleased with their decision to use our sd-rxRNA technology in combination with their TCR approach. The use of our immuno-oncology sd-rxRNA compounds with their receptor-modified T cells could potentially create a next generation of very powerful adoptive cell therapies against serious cancers that currently are difficult to target."

About Medigene’s TCR technology: The TCR technology aims at arming the patient’s own T cells with tumor-specific T-cell receptors. The receptor-modified T cells are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient’s tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient’s T cells outside the body (ex vivo).

TCR therapy is developed to utilize a higher number of potential tumor antigens than other T cell-based immunotherapies, such as chimeric antigen receptor T cell (CAR T) therapy. Medigene is preparing the clinical development of its first TCR candidates and is establishing a pipeline of recombinant T-cell receptors, and has established Good Manufacturing Practice (GMP)-compliant processes for their combination with patient-derived T cells.

Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard, TecDAX) is a publicly listed biotechnology company headquartered in Martinsried near Munich, Germany. The company is developing highly innovative immunotherapies to target various forms and stages of cancer. Medigene concentrates on the development of personalized T cell-based therapies, with associated projects currently in pre-clinical and clinical development.

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On December 11, 2017 Innovation Pharmaceuticals, (OTCQB:IPIX) ("the Company"), a clinical stage biopharmaceutical company, reported successful topline results from the Company’s randomized, double-blind, placebo-controlled, Phase 2 clinical trial of Brilacidin (see NCT02324335) for the prevention and control of Oral Mucositis (OM) in patients receiving chemoradiation for treatment of Head and Neck Cancer (Press release, Innovation Pharmaceuticals, DEC 11, 2017, View Source [SID1234522527]). Brilacidin-OM is being developed under an FDA Fast Track designation for this indication.

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Summary of Topline Results from the Placebo-Controlled Phase 2 Trial

· Brilacidin met primary endpoint of reduced incidence of severe OM experienced by patients during radiation therapy.
· Incidence of severe OM in Modified Intent to Treat (mITT) Population: Brilacidin 42.9%, Placebo 60.0%.
· Incidence of severe OM in Per Protocol (PP) Population: Brilacidin 36.8%, Placebo 60.0%.
· Trial results support continued and expedited development of Brilacidin-OM.

Clinical Trial Background

In this trial, Head and Neck Cancer patients self-administered Brilacidin (45 mg/15 ml oral rinse—"swish and spit") or placebo three times daily across 7 consecutive weeks (49 days). Of the 61 patients randomized, 46 patients met the cumulative radiation dose criteria of at least 55 Gy—the minimum treatment threshold for inclusion in the efficacy population—and 39 of these patients met more strict criteria for inclusion in the "per protocol" study population. The trial’s primary endpoint was established as reduced incidence of severe OM (defined as Grade ≥ 3 on the WHO Oral Mucositis scale) experienced by patients during radiation therapy.

Topline results reveal a clear reduction in the incidence of severe OM (WHO Grade ≥ 3) in patients treated with Brilacidin-OM as compared to those on placebo. Brilacidin also appeared generally safe and well-tolerated across all treated patients (the safety population).

Primary Efficacy Results: Incidence of severe OM (WHO Grade ≥ 3)

Active (Brilacidin) Control (Placebo)

Modified Intent to Treat 9 of 21 patients (42.9 %) 15 of 25 patients (60.0%)
(mITT) Population (n=46)
Per Protocol
(PP) Population (n=39) 7 of 19 patients (36.8%) 12 of 20 patients (60.0%)

Overall reduction in observed severe Oral Mucositis (WHO Grade ≥ 3) in the Brilacidin-OM treatment group from that seen in the control group ([incidence control – incidence active]/incidence control) was: 28.5% (mITT population) and 38.7% (PP population).

Safety and Tolerability Profile

Brilacidin administered as an oral rinse was generally well-tolerated by patients. Safety findings were typical for patients with Head and Neck Cancer being treated with chemoradiation, with all treated patients reporting at least one Treatment-Emergent Adverse Event (TEAE). Of the TEAEs categorized as serious (SAEs), 13 patients (8 in the Brilacidin group, and 5 in the Placebo group) experienced at least one SAE. No SAEs reported led to death. None of the SAEs were classified by the Investigator as related to Brilacidin.

Management Comments

Additional study endpoint analyses are ongoing, with outputs expected in the coming weeks. These endpoints are important in building a deeper knowledge base around Brilacidin-OM, further informing other aspects of efficacy and helping to plan the next stage of clinical development.

"The completion of the Phase 2 trial of Brilacidin-OM is a major milestone for the Company, particularly given the successful topline study results. In a broader context, these mid-phase study results represent a watershed moment in the management of OM, as there has been negligible prior innovation in safely mitigating the onset of the severest stages of the disease," commented Leo Ehrlich, Chief Executive Officer at Innovation Pharmaceuticals. "We believe that we now occupy a leadership position with this drug candidate in the prevention and treatment of severe OM in Head and Neck Cancer patients. Considering the global unmet medical need in treating severe OM, we anticipate leveraging these promising data, both in securing potential partnership opportunities and establishing an early competitive market position. In combination with other promising clinical data on Brilacidin, we are building a strong case that our novel defensin-mimetic pipeline can safely address an array of diseases and conditions by showing meaningful clinical responses. We now look forward to discussing our plans with the FDA to best align and prepare for the expedient advancement of the Brilacidin-OM program."

"Based on these data, we are confident Brilacidin-OM has potential to improve significantly the treatment paradigm for OM," said Arthur P. Bertolino, MD, PhD, MBA, President and Chief Medical Officer at Innovation Pharmaceuticals. "To see a clear beneficial clinical response is what clinicians hope for—a viable drug candidate bettering the lives of patients in dire need of newer treatment options. Further, today’s news is added validation of the Brilacidin Franchise, now anchored in three distinct clinical indications—OM, inflammatory bowel disease and serious skin infections. Brilacidin is an extremely unique drug candidate that we look forward to continuing to explore and advance across its many therapeutic applications."

About Brilacidin

Brilacidin is Innovation Pharmaceuticals’ lead drug candidate in its defensin mimetic franchise. Modeled after Host Defense Proteins (HDPs), the "front-line" of defense in the immune system, it is a small, non-peptidic, synthetic molecule that kills pathogens swiftly and thoroughly. Just as importantly, Brilacidin also functions in a robust immunomodulatory capacity, lessening inflammation and promoting healing. Due to its unique properties, the Company is studying Brilacidin’s effect on Oral Mucositis (under Fast Track designation) and on Ulcerative Proctitis / Proctosigmoiditis (UP/UPS) in Phase 2 trials. Additional trials of Brilacidin are planned in other conditions, including: Atopic Dermatitis, Hidradenitis Suppurativa and Acne. Brilacidin is also being developed under FDA’s Qualified Infectious Disease Product (QIDP) designation as an antibacterial product for Acute Bacterial Skin and Skin Structure Infection (ABSSSI)—qualifying it for Fast Track and possible Priority FDA Review and an extra 5 years of United States market exclusivity upon drug approval.

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About Brilacidin-OM

Innovation Pharmaceutical’s first-in-class immunomodulatory drug candidate, Brilacidin, targets the prevention of severe Oral Mucositis (OM)—a common and debilitating side-effect of receiving chemoradiation therapy—in Head and Neck Cancer. Each year, OM affects hundreds of thousands of patients worldwide. Only a limited number of OM treatments are available, most of which are palliative in nature. A Phase 2 randomized, placebo-controlled clinical trial of Brilacidin-OM (see NCT02324335) has been recently completed in which topline results demonstrate a reduced rate of severe OM (WHO Grade >3) in patients treated with Brilacidin-OM compared to those on placebo.

About Oral Mucositis

Oral Mucositis (OM) is a frequent, painful and debilitating complication of chemoradiation. Head and Neck Cancer (HNC) patients—comprising an estimated 65,000 newly diagnosed cases in the U.S. alone in 2017, and an estimated 700,000 worldwide (source: GLOBOCAN)—are at the greatest risk of developing OM (a 90 to 100 percent rate of occurrence). By 2030, the global incidence of HNC cases is expected to exceed 1 million per year. Moreover, between 25 and 60 percent of cancer patients, regardless of cancer type, also will experience OM. Characterized by inflammation and ulceration, patients suffering from OM are often unable to speak and eat (requiring the insertion of a feeding tube) and are more susceptible to infections, with severe cases leading to hospitalization at increased treatment costs of up to $25,000. There currently are no approved medications for the prevention of OM in the HNC population, with only limited palliative care options available. Worldwide, the potential market for OM is expected to exceed $1 billion in the next few years.

On December 11,2017 Immunocore Limited, the world’s leading TCR company focused on delivering first-in-class biological therapies that transform lives, reported that it has been informed by the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) that IMCgp100 has been granted Promising Innovative Medicines (PIM) designation for the treatment of patients with metastatic uveal melanoma(Press release, Immunocore, DEC 11, 2017, View Source [SID1234522505]).

PIM designation is an early indication that IMCgp100 is a promising candidate for the UK’s Early Access to Medicines Scheme (EAMS), intended for the treatment, diagnosis or prevention of metastatic uveal melanoma. This is based on early Phase I clinical trial data published at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting in November. IMCgp100 will be a suitable candidate for entry into Step II of the EAMS process, for which Immunocore is in a pivotal registrational clinical trial in patients with metastatic uveal melanoma. Following this, IMCgp100 will enter the EAMS scientific opinion assessment step.

For more information on clinical trials involving IMCgp100, please visit clintrials.gov.

James Sandy, Chief Development Officer at Immunocore, commented: "We are delighted by the MHRA’s decision to award PIM designation to IMCgp100, which gives us scope to accelerate the approval process for IMCgp100, and bringing us a step closer toward making IMCgp100 available for patients with uveal melanoma, for which there are currently no effective treatment options available."

IMCgp100 was granted Orphan Drug Designation by the US Food and Drug Administration (FDA) in January 2016 and participated in the EMA’s Adaptive Pathways Pilot Programme.

On December 11, 2017 Reata Pharmaceuticals, Inc. (Nasdaq:RETA) ("Reata" or "the Company"), a clinical-stage biopharmaceutical company, reported the presentation of interim data from the ongoing Phase 1b portion of the REVEAL study of omaveloxolone in combination with approved checkpoint inhibitor (CI) therapies, ipilimumab or nivolumab, for the treatment of Stage III or IV unresectable or metastatic melanoma (Press release, Reata Pharmaceuticals, DEC 11, 2017, View Source;p=RssLanding&cat=news&id=2322028 [SID1234522532]). The data were presented in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno Oncology Congress 2017 in Geneva, Switzerland by lead author Dr. Sapna Patel, Assistant Professor, Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center.

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All enrolled patients were required to have biopsy positive inducible nitric oxide synthase (iNOS), which is an independent predictor of poor survival in melanoma patients. Emerging translational data suggest that iNOS is a key mediator of myeloid-derived suppressor cells (MDSCs), whose presence has been shown to correlate with reduced activity of CIs. Of the 30 patients enrolled in REVEAL with evaluable tumor restaging, 7/30 (23%) of patients were checkpoint inhibitor-naïve, while 23/30 (77%) of patients were refractory to prior checkpoint inhibitor therapy. The overall response rate (confirmed + unconfirmed) observed in all evaluable patients was 8/30 (27%, 6 partial responses (PR) and 2 complete responses (CR)).

In CI-naïve patients, 4/7 (57%) had objective responses including 1 CR. 3/18 (17%) patients treated with omaveloxolone + nivolumab who were refractory to prior checkpoint inhibitor therapies had objective responses, including 1 CR. The majority of responses have been durable and are ongoing. Omaveloxolone treatment was associated with decreases in tumor iNOS, programmed death ligand 1 (PD-L1), and indoleamine 2,3-dioxygenase (IDO-1) expression. No serious AEs considered related to omaveloxolone have been reported to date. Commonly reported treatment-related adverse events included fatigue, nausea, pruritus, transaminase increases, and decreased appetite.

"The ongoing REVEAL trial data suggests that omaveloxolone may have activity in patients who are refractory to checkpoint inhibitors, which is an emerging and large unmet need," said Colin Meyer, M.D., Chief Medical Officer of Reata. "We are continuing with the dose escalation phase of the study to identify the optimal dose, and upon completion, we will determine the next steps in the clinical development program for omaveloxolone in melanoma."

On December 11, 2017 Actinium Pharmaceuticals, Inc. (NYSE American:ATNM) ("Actinium" or "the Company") reported positive preliminary data from its ongoing Phase 2 trial of Actimab-A in patients newly diagnosed with Acute Myeloid Leukemia (AML) who are over the age of 60 and not able to tolerate induction chemotherapy (Press release, Actinium Pharmaceuticals, DEC 11, 2017, View Source [SID1234522522]). Actinium Pharmaceuticals is a clinical-stage biopharmaceutical company focused on developing and commercializing targeted therapies for safer myeloablation and conditioning of the bone marrow prior to a bone marrow transplant, and for the targeting and killing of cancer cells. Actimab-A is an ARC or Antibody Radio-Conjugate comprised of the anti-CD33 antibody lintuzumab labeled with the alpha-emitting isotope Actinium-225. Actimab-A is the lead candidate from Actinium’s CD33 Program, which now includes two additional indications; Actimab-M in Multiple Myeloma and Actimab-MDS as a bridge to transplant in TP53 positive patients with Myelodysplastic Syndrome.

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Patients in the Phase 2 trial had an Overall Response Rate (ORR) of 69% when treated with 2.0 µCi/kg/fraction of Actimab-A administered as a single agent via two infusions administered on day 1 and day 8. In addition, patients that were evaluable had a median reduction in bone marrow blasts of 98%. Actinium had previously reported a 56% response rate in patients that were evaluable at time of the abstract submission when data were available on 9 patients compared to the 13 patients reported in the poster. The Phase 2 trial of Actimab-A is designed to enroll 53 patients, with a formal interim analysis scheduled when 31 patients have been enrolled with the target ORR for the study being thirty-five percent. This hurdle rate has been exceeded with the first thirteen patients treated at 2.0 µCi/kg/fraction and the number of responses needed at the interim analysis of 31 patients to progress the trial to the full 53 patients was also cleared in these initial 13 patients. Consequently, the Company has elected to continue the trial at a lower dose in order to develop the best therapeutic profile based on balancing the myelosupressive effect seen at 2.0 µCi/kg/fraction versus the efficacy seen at both the 2.0 µCi/kg/fraction (50% ORR in Phase 1 and 69% ORR in Phase 2) and the 1.5 µCi/kg/fraction (67% ORR in Phase 1). After making suitable protocol modifications the trial is again robustly enrolling patients who will now receive Actimab-A at 1.5 µCi/kg/fraction. This dose had the highest response rate of any dose cohort in the most recent Phase 1 trial of Actimab-A with patients receiving this dose having a 67% ORR.

Dr. Mark Berger, Actinium’s Chief Medical Officer, said, "It is incredibly exciting to see these high response rates and the huge reduction in bone marrow blasts from Actimab-A as a single agent, which I attribute to the targeting ability and potency of our ARC based approach. Having led the development and initial approval of Mylotarg, the only CD33 targeting agent approved in AML, I have since had tremendous interest in this field and today’s results confirm my initial inclination that Actimab-A has the potential to be highly differentiated and potentially best-in-class. In addition to these highly encouraging results, we have gained invaluable insights into the profile of Actimab-A that we will leverage to drive value going forward. Given that Actimab-A had a higher response rate of 67% at the 1.5 µCi/kg/fraction compared to a 50% response rate at 2.0 µCi/kg/fraction in our most recent Phase 1 trial, I am excited to be moving ahead with our new dose level, which I believe will be associated with strong efficacy, acceptable myelosuppression and meet the goals for the remainder of the study. Given Actimab-A’s highly differentiated mechanism of action, we believe it can be used synergistically with other treatments to increase efficacy but with minimal increase in toxicities."

Compared to other AML agents, very few possibly related extramedullary toxicities were observed with only two (pneumonia and septic shock) being observed in more than one patient, both of which were observed in two patients each. Importantly, no case of veno-occlusive disease, a potentially fatal complication of the liver that can preclude a patient from receiving a stem cell transplant, was observed in any of the patients. Grade 4 myelosuppression was observed in all evaluable patients.

Dr. Berger continued, "These additional data are consistent with previous data indicating that an anti-CD33 antibody labeled with Actinium-225 has minimal extramedullary toxicities and is highly potent. The combination of these factors has allowed us to pursue Actimab-MDS as a bridge to transplant for patients with myelodysplastic syndrome that have a genetic mutation of the TP53 gene. We are excited to leverage the strengths of the Actimab-A trial to expand the patient population that we can treat with this agent."

Sandesh Seth, Actinium’s Chairman and CEO, said, "In less than a year we have expanded our CD33 Program from a single asset, Actimab-A, to a full-fledged drug development program with the addition of Actimab-M and Actimab-MDS. This is early evidence of the potential of the newly infused talent and upgraded functionality that is being developed in the Company. We take comfort in the fact that now our team has enrolled more patients in our three trials in the second half of 2017 than the combined total enrollment in the four years prior. In 2018, we expect to have topline results with both Actimab-A and Actimab-M, in line with prior guidance, and also begin the newly announced Actimab-MDS trial. Our CD33 targeting ARC’s are showing promise to be utilized for both therapeutic and safer myeloablative purposes. Exemplifying the unique therapeutic promise of our CD33 targeting ARC’s compared to other modalities is the recent involvement of thought leader Dr. Gail Roboz and her consortium who will spearhead the new Actimab-MDS initiative. With these new data in hand, we look forward to continuing to develop our CD33 program as the leading one in the industry in 2018 and beyond."

About Actimab-A

Actimab-A, Actinium’s most advanced CD33 Program candidate, is currently in a multi-center, open-label Phase 2 trial for patients newly diagnosed with AML, age 60 and above, that are ineligible for standard induction chemotherapy. Actimab-A is being developed as a first-line therapy and is a monotherapy that is administered via two 30-minute infusions that are given 7 days apart. Actimab-A is an ARC or Antibody Radio-Conjugate that targets CD33, a protein that is expressed in virtually all patients with AML cells via the monoclonal antibody, lintuzumab, which carries the potent cytotoxic radioisotope Actinium-225 to the AML cancer cells. Actinium-225 gives off high-energy alpha particles as it decays, which kill cancer cells and as actinium-225 decays it produces a series of daughter atoms, each of which gives off its own alpha particle, increasing the chances that the cancer cell will be destroyed by crossfire. Actimab-A is a second-generation therapy from the Company’s CD33 Program, which was developed at Memorial Sloan Kettering Cancer Center and has now been studied in over 100 patients in four clinical trials. Actimab-A has been granted Orphan Drug Designation for newly diagnosed AML in patients 60 and above by the U.S. Food and Drug Administration and the European Medicines Agency.