On November 20, 2015 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) (Aptose or the Company), a clinical-stage company developing new therapeutics and molecular diagnostics that target the underlying mechanisms of cancer, reported that the Food and Drug Administration (FDA), following a voluntary suspension of dosing by the Company and discussions with the Company, placed the Phase Ib clinical trial of APTO-253 in patients with hematologic cancers on clinical hold (Press release, Aptose Biosciences, NOV 20, 2015, View Source;p=RssLanding&cat=news&id=2114349 [SID:1234508462]). This hold is intended to ensure patient safety on the trial and to ensure manufacturing and dosing procedures are consistent with the appropriate documented quality standards.

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The voluntary suspension of dosing by the Company was initiated as a result of a planned preliminary review, which was accelerated to evaluate manufacturing processes and procedures upon the report of an operational difficulty with an IV infusion pump at a clinical site. The pump experienced back pressure during IV patient dosing at the point of the filter. Further review discovered preliminary concerns regarding the documentation records of the manufacturing procedures of the drug product associated with APTO-253.

The Company stated that a complete safety review of all patient files had been completed prior to initial discovery of the manufacturing documentation irregularities, and there have been no drug-related serious adverse events (SAEs) reported. The observed pharmacokinetic levels in the patients treated were within the expected range.

"We are disappointed by these events and have engaged an independent third party review. Importantly, this finding does not undermine the positive safety profile that APTO-253 has demonstrated in clinical development, and we remain confident in its potential as a promising therapeutic option for patients with acute myeloid leukemia and other hematologic malignancies," said William G. Rice, Ph.D., Chairman, President and CEO. "While we expect some delay in the clinical trial, we are committed to ensuring that upon re-initiation of clinical dosing the drug product is of the highest standards. We plan to provide updated timeline guidance as soon as practical."

Key Points:

An internal review identified potential documentation irregularities and the Company voluntarily and immediately suspended dosing of patients out of an abundance of caution to ensure safety.

Aptose currently possesses a sufficient supply of API to create fresh batches of drug product for the resumption of clinical dosing upon FDA approval and guidance.

New contract manufacture organizations have been identified to manufacture fresh batches of cGMP clinical supply upon completion of investigation and in coordination with FDA guidance.

Overall effect to the Phase Ib trial timeline is expected to be partially mitigated by initiation of the new trial sites and updated timeline will be reported as soon as determined.

On November 20, 2015 Kancera reported its Interim Report for Kancera AB (publ) Q3 2015 (Press release, Kancera, NOV 20, 2015, View Source;releaseID=1076341 [SID:1234508315]). January 1 – September 30, 2015.

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The period January to September 2015 and the third quarter 2015 in brief

R&D expenses for the period amounted to SEK 12.1m (SEK 9.6m) of which the third quarter constituted SEK 3.2m (SEK 2.7m).

Operating income for the period amounted to SEK -13.8m (SEK -11.0m) of which the third quarter constituted SEK -3.4m (SEK -3.1m).

Income after financial items for the period amounted to SEK -13.7m (SEK -10.9m) of which the third quarter constituted SEK -3.4m (SEK -3.0m).

Earnings per share for the period were SEK -0.14 (SEK -0.13) of which the third quarter constituted SEK -0.03 (SEK -0.03).

Cash flow from operating activities for the period amounted to SEK -16.0m (SEK -11.6m) of which the third quarter constituted SEK -5.1m (SEK -4.4m).

Equity as of September 30, 2015 amounted to SEK 27.8m (SEK 31.6m) or SEK 0.27 (SEK 0.32) per share. The equity/assets ratio as of September 30, 2015 was 74 percent (77 percent).

Cash and cash equivalents as of September 30, 2015 amounted to SEK 20.2m (SEK 27.5m).
Significant events during the period

Kancera reported that a second efficacy study of the drug candidate KAN0439834 has been completed in an animal model of an advanced stage of chronic lymphocytic leukemia characterized by a genetic change which makes the disease more difficult to treat. The results show that KAN0439834 reduces the number of ROR expressing leukemia cells in the lymphatic system (spleen) after 14 days of treatment. Further, Kancera reported that a second patent application EP15153394.0 has been filed covering small-molecule ROR inhibitors, including the drug candidate KAN0439834.

Kancera reported that the patent WO 2011/079902 concerning monoclonal antibodies against ROR1 has been approved in China. Kancera has acquired partial rights to this patent from Bioinvent under an agreement that does not involve any financial burden for Kancera (except patent expenses) before revenues are generated. Kancera through the company’s co-founder Professor Håkan Mellstedt has been involved in the development of these antibodies. These antibodies have mainly been used to identify and validate new indications for a future ROR-inhibiting drug. Any further development of the ROR-targeted monoclonal antibodies for therapeutic purposes will only be done in a partnership that provides funding and access to expertise in development of antibody-based drugs.

Kancera reported an operational update of the cancer projects ROR, PFKFB3, and HDAC6.

The ROR project reported that that Kancera’s candidate drug KAN0439834 is effective against both leukemic cells circulating in the blood and leukemic cells that have invaded the lymph nodes in humans.

Recent studies of clinical samples from leukemia patients underscore that ROR inhibitors mainly target the white blood cells causing cancer while the healthy white blood cells, including T cells, are spared. These results are of significance for the possibility to combine ROR inhibitors with the new generation of immuno-stimulating cancer drugs that have been developed since the effect of those requires functional T-cells.

A new generation of ROR inhibitors is being developed against solid tumors.

The PFKFB3 project reported a new discovery showing that Kancera’s PFKFB3 inhibitor KAN0438757 kills cancer cells by preventing them to repair their DNA. The discovery indicates that KAN0438757 could be an efficient complement to radiation for the treatment of advanced cancer.

The HDAC6 project reported that Kancera’s HDAC6 inhibitors counteract the migration of cancer-associated fibroblast cells and that an international patent application was filed in May.

Kancera’s Annual General Meeting on May 28, 2015 decided to re-elect the current Board of Directors and auditor (Ernst & Young). The General Meeting also decided to authorize the Board, on one or more occasions until the next Annual General Meeting, to issue new shares. A new share issue may be made with or without preferential rights and against cash payment and / or in kind or set-off. The purpose of the authorization and the reason for the deviation from shareholders’ preferential rights is to enable the acquisition of capital for corporate acquisitions and the company’s operation. If the share issue is made against cash payment and without preferential rights for the shareholders, the number of shares issued may not exceed ten percent of the total number of shares outstanding at the time the authorization is exercised.

Kancera announced that a new share issue, with the authorization of the Annual General Meeting in 2014, was closed on May 27, 2015. The issue comprised a maximum of 4,927,386 shares. In total 25,926,793 shares were signed, of which 4,644,304 with preferential rights (with the support of subscription rights) and 21,282,489 without preferential rights. The share issue was thus oversubscribed to about 500 percent. This issue raised Kancera AB approximately SEK 12.3m before issue costs.

Kancera announced that the first subscription period for the exercise of the employee warrants was closed in June 2015. In total 450,246 new shares were signed giving Kancera SEK 1.7m before issue costs. There remain 2,349,754 warrants, of which 560,000 are held by Kancera to cover social security costs that are part of the employee warrants program.

Kancera announced that the company’s HDAC6 project has been awarded a grant totaling SEK 2m from the Swedish innovation agency VINNOVA. The grant is directed to projects that can develop into new strong innovations in a range of common diseases, including cancer. The grant is paid on four occasions during the two-year project. The project will be implemented in collaboration with the Cancer Center Karolinska (CCK), and is also planned to involve Swedish companies such as SARomics Biostructures, MetaSafe and Adlego Biomedical.

Kancera announced that the company has entered into an agreement with Acturum Life Science AB in order to evaluate and further develop the unique Fractalkine receptor antagonist AZD8797. Based on published research that supports that the Fractalkine receptor antagonist may have a central role in different cancer forms, Kancera will evaluate how efficiently the Fractalkine receptor antagonist AZD8797 may stop tumor growth and relieve severe cancer pain. The agreement with Acturum Life Science gives Kancera right to evaluate AZD8797 in preclinical studies and then to acquire the project. This agreement entails no expenses for Kancera apart from investments in the patent portfolio and in the scientific evaluation. If Kancera chooses to acquire the Fractalkine project, following the preclinical evaluation phase, the total payment to Acturum will consist of 6 million Kancera shares divided into three tranches, which are due at pre-defined success-milestones.

Kancera provided an operational update on the ROR and Fractalkine projects:

In the ROR project, Kancera reported that follow-up studies of the pharmaceutical properties of KAN0439834 show that they probably are better than previously assumed with respect to uptake and penetration of the substance to the cancer. The new studies indicate that dosing 2-3 times a day at 65-300 mg gives a concentration in the body that may be sufficient to exert an effect on solid tumors. Against this background, ROR inhibitors will be tested in animal models of solid tumors. It was further reported that ROR inhibitors have shown effect against leukemic cells from bone marrow which is a capacity wanted since the existing drugs are not sufficiently effective against cancer cells in the bone marrow.

In the Fractalkine project, Kancera reported that a network of leading cancer and pain scientists that has been established that will evaluate the drug candidate KAN0440567 (AZD8797) in an advanced animal model closely resembling the human form of pancreatic cancer. Kancera has synthesized and quality controlled the salt form of the drug candidate that will be used in this study and has conducted a successful peroral dosing study in mice.

Significant events after the end of the reporting period

Kancera provided an operational update for the PFKFB3 and HDAC6 projects as well as the EU-funded epigenetically targeted parasitic project A PARADDISE.

After the end of the period, Kancera reported from the collaboration with Prof. Thomas Helleday that Kancera’s PFKFB3 inhibitor significantly reduces the size of a tumor formed by aggressive human breast cancer cells (called triple negative breast cancer cells) transplanted into zebrafish. The results from the study support that Kancera’s PFKFB3 inhibitor is effective against these aggressive cancer cells if the substance reaches the tumor at a sufficient concentration, which is easier to achieve in zebrafish compared to e.g. in mice.

Kancera has developed several chemical families of potent and selective HDAC6 inhibitors based on a common scaffold, and it is now reported that Kancera has decided to withdraw the original patent from 2014 in order to postpone the publication of the structures at least 12 months. This is done in order to prevent that Kancera’s existing patent application becomes an obstacle to a new supplementary patent application that will include the newly developed HDAC6 inhibitors.

In June 2015, Vinnova announced that a grant was awarded to Kancera to support the further development of HDAC6 inhibitors against cancer. The first installment of the grant was then paid in July. Vinnova has now decided to bring forward the second installment (SEK 750, 000) to the HDAC6 project.

In February 2014 Kancera received an initial payment from the EU amounting to € 523,655 for the execution of the A-PARADDISE project. The project has now issued an interim report which 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.

Statement from the CEO

On November 11, Kancera appeared on the front page of the international trade journal "Bioworld" (View Source). The news item concerned Kancera’s new Fractalkine project that aims to help the immune system to attack the cancer. The study is performed using a drug candidate that was originally developed by AstraZeneca against the autoimmune disease multiple sclerosis (MS). The effect of this drug candidate against an MS-like disease in animals has convinced us that it is effective. The question we are now asking in the ongoing studies is if the same mechanism of action that is effective against MS also can help against intractable cancers. The risk in this cancer project is high as usual, but the scientific literature suggests that there is a realistic chance of success. The study is performed in collaboration with the FAM-owned Acturum Life Science AB which through an agreement has given Kancera an exclusive right to evaluate and later acquire this drug candidate.

In the ROR project, we have learnt more about how the first drug candidate KAN0439834 is expected to work in humans. The results of these calculations, partly based on animal studies and partly on comparative studies of chemically similar drugs, suggest that we can achieve a concentration in the blood that is effective against leukemia and possibly also against solid tumors. As is often the case in drug development, a problem encountered is that even if the drug candidate appears to have good properties in humans, efficacy has to be shown in a rodent disease model before clinical studies and in rodents drugs are often broken down too quickly. We are now testing two ways past this challenge; one where we stop the breakdown of the compound in the rodent by means of a drug-like substance, and one where we study the effect on tumors in zebra fish where it is possible to set the concentration of the drug to the level that is expected to be achieved in humans. In the autumn’s big biotech meeting "Bio Europe", which this year took place in Munich in November, it was clear that several large pharmaceutical companies now are using the zebra fish model as a step between cell studies and studies in rodents and humans.

We have also conducted the first cancer study with a PFKFB3 inhibitor in zebrafish in collaboration with Prof. Thomas Helleday. The study was performed using human tumor cells from a treatment-resistant breast cancer (so called triple negative breast cancer) and showed that Kancera’s PFKFB3 inhibitor significantly slows the development of tumor cells. These results are currently particularly relevant since this effect is coupled to this year’s Nobel Prize in chemistry, where one recipient was Tomas Lindahl for his discoveries about how cells are able to repair their DNA. It is thanks to the discoveries behind this Nobel Prize that Kancera in collaboration with Prof. Thomas Helleday’s group at the Karolinska Institute has been able to show that our PFKFB3 inhibitors can beat the cancer by preventing the repair of its genome.

During the Bio Europe meeting in Munich, Kancera presented the project portfolio during a session dedicated to cancer companies and had individual meetings with pharmaceutical companies from Europe, USA and Japan. At these meetings, we received a positive response regarding the progress in the company’s portfolio of cancer projects.

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.