On November 20, 2015 Aduro Biotech, Inc. (Nasdaq:ADRO), a clinical-stage immunotherapy company, reported the presentation of an overview of novel antibody and combination strategies designed to stimulate durable anti-tumor response at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Symposium on Immuno-Oncology 2015, taking place November 20-21, 2015, in Lausanne, Switzerland (Press release, Aduro BioTech, NOV 20, 2015, View Source;p=RssLanding&cat=news&id=2114366 [SID:1234508296]). The presentation was featured in a keynote lecture delivered at the ESMO (Free ESMO Whitepaper) symposium by Andrea van Elsas, Ph.D., chief scientific officer of Aduro Biotech Europe, titled, "Immunomodulatory Antibodies Beyond PD-1."

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The presentation focused on advancements in the field of immuno-oncology involving combination antibody approaches targeting T cells (e.g. CD27 agonists), the tumor-immune interfaces (e.g. CD47 – SIRP(alpha) axis), dendritic cells and macrophages and bispecific antibodies. Dr. van Elsas also discussed promising early work with new agonists such as cyclic dinucleotides (CDNs).

"Recent advances in immunotherapy are bringing about a new era of cancer medicine and revolutionizing the development of novel treatments across a broad range of cancer types," said Dr. van Elsas. "Checkpoint inhibitors have clearly demonstrated clinical benefit as single agent therapy in some patient populations, but emerging data suggests combination therapy may be required to extend this benefit to a majority of patients. At Aduro, our focus is on advancing multiple therapeutic approaches that have the potential to yield powerful immunotherapy combinations."

During the presentation, Dr. van Elsas summarized the three diverse immunotherapy platforms that Aduro focuses on that aim to disrupt the tumor microenvironment and harness patients’ immune systems to fight multiple cancer targets:

– LADD (live, attenuated, double-deleted Listeria mononcytogenes) involving bacteria-based mobilization of the immune system

– CDNs targeting small molecule activation of the Stimulator of Interferon Genes (STING) receptor leading to T cell priming specific for tumor neoantigens

– B-select technology targeting first or best-in-class agonist and antagonist monoclonal antibodies (mAbs)

Additionally, key topics that were highlighted in the presentation included:

– Preclinical data demonstrating potent anti-tumor activity of ADU-S100, a proprietary molecule based on Aduro’s CDN platform technology

– ADU-S100’s ability to induce innate immunity through STING, a critical receptor to activate immune cells including dendritic cells in the tumor microenvironment

– The formulation of ADU-S100 with GVAX into the cancer vaccine – "STINGVAX" – that was shown to be active in anti-PD1 resistant tumors. GVAX is a family of cancer immunotherapies acquired by Aduro in 2013

– Research demonstrating mode-of-action of CD27 agonistic antibodies

– Research demonstrating how antibodies that block CD47 – SIRP(alpha) interaction to enhance tumor killing and rejection as well as elicit functional cytotoxic T lymphocytes (CTL)

Aduro believes this research underscores the critical importance of not only overcoming immune suppression, but also activating and stimulating the immune system using Aduro’s CDN approach targeting the STING receptor and Aduro’s LADD-based immunotherapies.

On November 20, 2015 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported the Company has submitted an IND application to the U.S. Food and Drug Administration (FDA) and plans to initiate a Phase 2 breast cancer study in the U.S. as soon as possible (Press release, Spectrum Pharmaceuticals, NOV 20, 2015, View Source [SID:1234508297]).

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"This Phase 2 study is an important step for us to solidify our registration strategy in the U.S.," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "The potential target market for Poziotinib is large, and metastatic breast cancer patients continue to progress despite availability of several drugs. Poziotinib has shown promising early clinical activity in Phase 1 trials in patients who had failed multiple lines of treatment including the HER2-directed therapies, trastuzumab and lapatinib. The U.S. Phase 2 trial was designed based on learnings from Phase 1 and Hanmi’s ongoing Phase 2 trials in Korea. We are planning a fast to market strategy as a single agent in parallel with the development of a broader indication using poziotinib in combination with other approved therapies for use in earlier stage disease."

The Phase 2 study is planned to be an open-label study that will enroll approximately 70 patients with HER-2 positive metastatic breast cancer, who have failed at least one or more HER-2 directed therapy. The dose and schedule of oral poziotinib will be based on clinical experience from the studies in Korea, and in addition include the use of prophylactic therapies to help minimize known side-effects of HER2-directed therapies.

Poziotinib is a novel, oral pan-HER inhibitor that irreversibly blocks signaling through the Epidermal Growth Factor Receptor (EGFR, HER) Family of tyrosine-kinase receptors, including HER1 (erbB1; EGFR), HER2 (erbB2), and HER4 (erbB4), and importantly, also HER receptor mutations; this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, gastric cancer, etc. Currently, poziotinib is being investigated by Hanmi in several mid-stage trials in different solid tumor indications including EGFR-mutant NSCLC, gastric cancer, head & neck cancer and HER2 positive breast cancer.

On November 20, 2015 ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT:IMUC) reported the presentation today of recently updated overall survival (OS) results and immune response data from the phase 2 trial of ICT-107 in patients with newly diagnosed glioblastoma (Press release, ImmunoCellular Therapeutics, NOV 20, 2015, View Source [SID:1234508298]). ICT-107 is a dendritic cell-based immunotherapy targeting multiple tumor-associated antigens on glioblastoma stem cells. The data are being presented at the 20th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology, being held in San Antonio, TX. The data from the phase 2 trial continue to indicate a survival advantage in the ICT-107 treated group compared to the control group. The data also show a significant association between immune response and survival, especially in HLA-A2 positive (HLA-A2+) patients, which is the target patient population for the phase 3 registration trial.

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IOS results were analyzed at three years after the last patient enrolled. For the 124-patient intent-to-treat population (ITT), median OS was 1.6 months or 10% better for ICT-107 patients than control. The difference in the Kaplan-Meier (KM) survival curves for this patient population was not statistically significant.

Updated OS results for the pre-specified subgroup of HLA-A2+ patients continue to support selecting this patient population alone for a well powered phase 3 trial. For the MGMT methylated, HLA-A2+ PP population, median OS was 13.8 months or 58% better for ICT-107 treated patients than control. For the MGMT unmethylated, HLA-A2+ per-protocol (PP) population, median OS was 4.0 months or 34% better for ICT-107 treated patients than control. The differences in the KM survival curves for these two pre-specified phase 2 sub-populations were not powered for, and did not achieve, statistical significance.

ELISPOT evaluation of antigen-specific immune response demonstrated a more frequent immune response in HLA-A2+ patients compared with HLA-A1 patients, and this difference was statistically significant. This increased immune response in HLA-A2+ patients further supports the selection of HLA-A2+ patients exclusively for inclusion in the phase 3 trial.

In HLA-A2+ patients, immune response was shown to be associated with survival. 60% of ICT-107 treated patients demonstrated a statistically significant immune response compared to only 36% of control patients. In a KM comparison of OS for immune responders versus non-responders, the responder curve showed a statistically significant survival benefit with a log-rank p-value of 0.0084. For ICT-107 treated patients, the KM comparison of OS for responders versus non-responders showed a statistically significant survival benefit with a log-rank p-value of 0.0147. The Company believes that the relationship between immune response and OS supports the phase 3 design improvement of adding more ICT-107 doses for patients in the first year of the protocol.

Immune response did not differ statistically for MGMT methylated compared to unmethylated patients. This result supports including both MGMT types of patients in phase 3 testing.

Of particular interest was the unexpected finding that there was an increased immune response in some control patients post-treatment. One potential explanation is that the phase 2 control (activated dendritic cells without peptide loading) was immunologically active. The phase 3 design employs a different control comprising the patients’ own monocytes, which are less immunologically active than dendritic cells. This control could help clarify a potential survival difference between ICT-107 and control treated patients.

The data are being presented at SNO by John S. Yu, MD, Founder of ImmunoCellular Therapeutics. Dr. Yu commented: "The final data from the phase 2 trial continue to demonstrate the therapeutic value of ICT-107 as a potential treatment for patients with newly diagnosed glioblastoma, and strongly support advancing to phase 3 testing. The clear association between immune response and survival is an important finding that we believe validates the immunotherapeutic mechanism of ICT-107 and strengthens our optimism for the phase 3 trial."

Andrew Gengos, ImmunoCellular Chief Executive Officer, said: "Based on these newly updated phase 2 survival results and the supporting immune response data, we are confident of the design improvements we have built into the phase 3 trial, and look forward to treating our first patient in the coming weeks. The phase 3 trial initiation represents a major milestone in the company’s path toward building a leading cancer immunotherapy company."

Phase 3 Registration Trial Sites Open; First Patient Anticipated to be Treated Soon

The phase 3 registrational trial of ICT-107 is designed as a randomized, double-blind, placebo-controlled study of over 400 HLA-A2+ subjects, which will be conducted at about 120 sites in the US, Canada and the EU. The primary endpoint in the trial is overall survival, which the FDA and EU regulators have stated is the appropriate endpoint for registrational clinical studies in glioblastoma. Secondary endpoints include progression-free survival and safety, as well as overall survival in the two pre-specified MGMT subgroups.

Multiple clinical trial sites have been opened for patient enrollment in the US, with additional sites anticipated to open in Canada and Europe in the coming weeks and months.

ImmunoCellular has reached agreement with the US FDA on a Special Protocol Assessment (SPA) relative to the primary and secondary endpoints as well as the statistical plan for the phase 3 trial. ImmunoCellular has also been awarded a $19.9 million grant from the governing Board of the California Institute for Regenerative Medicine (CIRM), California’s stem cell agency, to implement the phase 3 registration trial.

Background on the ICT-107 Phase 2 Trial

The ICT-107 phase 2 trial was a randomized, double-blind, placebo-controlled phase 2 study of the safety and efficacy of ICT-107 in patients with newly diagnosed glioblastoma multiforme following resection and chemoradiation. ICT-107 is an intradermally administered autologous immunotherapy consisting of the patient’s own dendritic cells pulsed with six synthetic tumor-associated antigens: AIM-2, MAGE-1, TRP-2, gp100, HER-2, IL-13Rα2. The placebo control consisted of the patient’s unpulsed dendritic cells.

A total of 124 patients were randomized at 25 clinical trial sites in the US. One third of the patients or 43 patients were treated with placebo, and the treatment arm included two thirds or 81 patients. All patients in the trial received standard-of-care temozolomide. The regimen was four induction doses of ICT-107 after chemoradiation, and then maintenance doses until the patient progresses. The primary endpoint of the trial was OS, defined as the time from randomization until date of death or the last date the patient is known to be alive. Secondary endpoints included PFS, defined as the time from randomization until the date of documented progressive disease or death, whichever occurs first, or the last date the patient is known to be alive and progression-free if progression or death is not observed. Other secondary endpoints included the rates of OS and PFS at six months after surgery, then assessed every three months until the end of the study. Safety and immune response were additional secondary endpoints.

For patients, families and physicians seeking additional information about the ICT-107 phase 3 trial, please consult www.clinicaltrials.gov.

On November 20, 2015 Kancera reported an operational update on the PFKFB3 and HDAC6 projects as well as the EU-funded epigenetically targeted parasitic project A-PARADDISE (Press release, Kancera, NOV 20, 2015, View Source;releaseID=1076542 [SID:1234508302]).

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The PFKFB3 project
Recent studies conducted within the framework of the collaboration with Prof. Thomas Helleday show that treatment with Kancera’s PFKFB3 inhibitor KAN0438757 alone inhibits an aggressive breast cancer tumor formed by the cell line MB231 (triple negative breast cancer). The human cancer cells were transplanted into zebra fish and four days treatment with KAN0438757 reduced the size of the tumor by more than 50% in comparison with the control treatment. The results support that Kancera’s PFKFB3 inhibitor is effective when reaching the tumor in sufficient concentration. Previously reported results show that Kancera’s PFKFB3 inhibitor KAN0438757 is able to counteract cancer cell repair of the DNA. Hence there are grounds to examine whether a more potent effect of PFKFB3 inhibitors can be achieved against triple negative breast cancer by combining the treatment with e.g. DNA damaging radiation. However, such a combination effect remains to be demonstrated in vivo.

The HDAC6 project
Since May 2015, when Kancera’s first patent application in the HDAC6 project entered the international stage, new series of potent and selective inhibitors of the enzyme has been developed. An additional patent application that covers these new HDAC6 inhibitors will be registered before the end of January, 2016. In order facilitate the filing of the new patent application, Kancera has decided to postpone the publication of the first patent application for one year.

In June 2015, Vinnova announced that Kancera’s HDAC6 project had been awarded a grant of SEK 2,000,000 for the further development of HDAC6 inhibitors against cancer. The first installment of SEK 436,000 was paid in July. Vinnova has now decided to bring forward the second installment of SEK 750,000 to December 2015.

EU projektet mot parasitsjukdomar – A-PARADDISE
In February 2014 Kancera received an initial payment from the EU amounting to € 523,655 for the execution of the A-PARADDISE project. This project is a collaboration between 15 research groups on three continents to develop drugs against severe parasitic diseases: malaria, schistosomiasis, leishmaniasis and Chagas disease. The project issued an interim report which now has been approved by the EU. This means that a further installment of the grant will be paid to Kancera at year-end according to plan. This installment amounts to € 285,000.

For further information, please contact,

Thomas Olin, CEO: +46 (0) 735 20 40 01
Address:
Kancera AB (publ)
Karolinska Institutet Science Park, Banvaktsvägen 22
SE 171 48 Solna

Please visit the company website; View Source

About the PFKFB3 project
By blocking mechanisms which enable the cancer cells to adapt to periods of oxygen deprivation, possibilities open for new treatment strategies. Kancera’s project is based on a specific inhibition of the enzyme PFKFB3 resulting in a decreased metabolism in cancer cells, and decreased cell growth. In addition, research shows that PFKFB3 is involved in the regulation of both angiogenesis and division of cells, two critical processes that contribute to tumor growth. PFKFB3 is more common in oxygen-deficient tumor tissue compared to healthy tissue, which makes a targeted effect therapy with fewer side effects than traditional chemotherapy possible. Inhibition of PFKFB3 is expected to starve and weaken the tumor cells by reducing their glycolysis and cell division. This is a way to overcome the current problems of tumor resistance to radiation and chemotherapy.

About the HDAC6 project
Histone deacetylases (HDACs) are primarily involved in removing acetyl groups from the so-called histones and thereby affect how our genes are stored and activated in the cell nucleus. Some HDACs also affect the cell function outside the cell nucleus. HDAC6 belongs to this group of HDACs with a major biological role in the regulation of the cancer cell´s ability to migrate and to form metastases. The use of HDAC inhibitors in the treatment of cancer patients has so far yielded promising results, but has been limited due to severe side effects. For this reason, the pharmaceutical industry is now looking for more selective inhibitors of individual HDAC enzymes. Kancera´s discovery of selective HDAC6 inhibitors may provide a solution on how health care could take advantage of the anti-cancer effects of HDAC inhibitors without causing the patient severe side effects.

About the EU-project against parasitic diseases – A-PARADDISE
A-PARADDISE (Anti-Parasitic Drug Discovery in Epigenetics) is an EU-funded project (contract n° 602080), which aims to identify new drug targets for anti-parasitic drug discovery as well as to develop already available lead compounds to candidate drugs against schistosomiasis. The project will also develop lead compounds and possibly drug candidates against targets in the following parasites (diseases): Leishmania (Leishmaniasis), Trypanosoma cruzi (Chagas disease) and Plasmodium falciparum (malaria). The A-PARADDISE project builds on the completed and highly successful SEtTReND project which was focused against schistosomiasis.

On November 20, 2015 the U.S. Food and Drug Administration reported that it has granted approval for Ninlaro (ixazomib) in combination with two other therapies to treat people with multiple myeloma who have received at least one prior therapy (Press release, , NOV 20, 2015, View Source [SID:1234508303]).
Multiple myeloma is a form of blood cancer that occurs in infection-fighting plasma cells (a type of white blood cell) found in the bone marrow. These cancerous cells multiply, produce an abnormal protein and push out other healthy blood cells from the bone marrow. The disease may result in a weakened immune system and cause other bone or kidney problems. The National Cancer Institute estimates there will be 26,850 new cases of multiple myeloma and 11,240 related deaths in the United States this year.

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"As we learn more about the underlying biology of multiple myeloma, we are encouraged to see the development of new ways to treat this disease," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research. "Today’s approval is the third drug for multiple myeloma approved this year and provides patients with a new oral treatment that slows disease progression when other therapy has failed." The FDA approved Farydak (panobinostat)in February and Darzalex (daratumumab) earlier this month.

Ninlaro is a type of cancer drug called a proteasome inhibitor and works by blocking enzymes from multiple myeloma cells, hindering their ability to grow and survive. Ninlaro is the first oral proteasome inhibitor and is approved in combination with another FDA-approved treatment for multiple myeloma called Revlimid (lenalidomide) and dexamethasone (a type of corticosteroid).

The safety and efficacy of Ninlaro were demonstrated in an international, randomized, double-blind clinical trial of 722 patients whose multiple myeloma came back after, or did not respond to, previous treatment. Study participants received either Ninlaro in combination with lenalidomide and dexamethasone or placebo plus lenalidomide and dexamethasone. Those taking Ninlaro lived longer without their disease worsening (average 20.6 months) compared to participants taking the other regimen (14.7 months).

The most common side effects of Ninlaro are diarrhea, constipation, low blood platelet count (thrombocytopenia), peripheral neuropathy (numbness and pain from nerve damage, usually in the hands and feet), nausea, peripheral edema (fluid under the skin causing swelling), vomiting and back pain.

The FDA granted priority review and orphan drug designations for Ninlaro. Priority review status is granted to applications for drugs that, if approved, would be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as tax credits, user fee waivers, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

Ninlaro is marketed by Takeda Pharmaceuticals based in Osaka, Japan. Farydak is marketed by East Hanover, New Jersey-based Novartis Pharmaceuticals. Darzalex is marketed by Janssen Biotech of Horsham, Pennsylvania. Revlimid is marketed by Celgene Corporation, based in Summit, New Jersey.