On January 25, 2018 Cotinga Pharmaceuticals Inc. (formerly Critical Outcome Technologies Inc.) (TSX VENTURE:COT)(OTCQB:COTQF) ("Cotinga" or the "Company"), a clinical-stage pharmaceutical company advancing a pipeline of targeted therapies for the treatment of cancer, reported the publication of positive data from a preclinical study demonstrating that combining COTI-2 with commonly used chemotherapeutic agents improves efficacy and exhibits a favorable drug resistance and toxicity profile in human cancer cell lines (Press release, Cotinga, JAN 25, 2018, View Source [SID1234533159]). These results were published in PLOS ONE under the title, Novel anti-cancer drug COTI-2 synergizes with therapeutic agents and does not induce resistance or exhibit cross-resistance in human cancer cell lines. The article may be found at the following link: View Source

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"These data support our rationale to evaluate COTI-2 as a combination therapy, and we are encouraged that these results specifically suggest that COTI-2 may be safe and efficacious in a variety of oncology indications when administered alongside the standard of care" said Richard Ho, Chief Scientific Officer. "In addition to data indicating synergistic activity against multiple cancer cell lines, the favorable drug resistance and toxicity profiles elucidated in this study are key findings that support the continued development of COTI-2 as part of a combination cancer therapy regimen. We look forward to building on these positive preclinical results as we advance combination treatment with COTI-2 into the clinic later this year."

The preclinical study, performed by Cotinga researchers and academic collaborators, evaluated COTI-2 in combination with commonly used chemotherapeutic agents through in vivo and in vitro experiments using human cancer cell lines. The study found that combining COTI-2 with commonly used chemotherapeutic agents, particularly taxanes and platins, demonstrated enhanced cytotoxic activity and tumor growth inhibition in a variety of human cancer cell lines. Combination treatment with COTI-2 did not induce drug resistance, and drug-resistant cancer cell lines showed little or no cross-resistance to COTI-2. The various combination treatment regimens evaluated did not result in any overt signs of toxicity.

Subject to sufficient financing, Cotinga plans to initiate basket, combination, and expansion studies in multiple oncology indications in 2018.

The Company is also continuing to analyze results from the gynecological arm of its Phase 1 trial of COTI-2 and expects to provide an update when further data are available in the first quarter of 2018. In addition, Cotinga is currently enrolling patients in the head and neck squamous cell carcinoma (HNSCC) dose-escalation arm of its Phase 1 trial of COTI-2, and expects to report initial safety data in the second quarter of 2018.

Effect of intratumoral (IT) injection of the toll-like receptor 4 (TLR4) agonist G100 on a clinical response and CD4 T-cell response locally and systemically (Poster, Immune Design, JAN 25, 2018, View Source [SID1234524042]). 2018 ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium. Abstract #71.

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On January 25, 2018 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a biotechnology company discovering and developing innovative immuno-oncology protein therapeutics, reported that a development milestone for cabiralizumab has been achieved, triggering a $25 million payment from Bristol-Myers Squibb Company (BMS, NYSE:BMY) under the license and collaboration agreement between the companies established in 2015 (Press release, Five Prime Therapeutics, JAN 25, 2018, View Source [SID1234523577]). The milestone was triggered by initiation of a multi-arm Phase 2 clinical trial (NCT03336216), sponsored by Bristol-Myers Squibb Company, evaluating cabiralizumab and Opdivo (nivolumab) with and without chemotherapy in patients with advanced pancreatic cancer.

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"Effective treatment for patients with pancreatic cancer remains a significant unmet need and is a cancer for which existing immunotherapies have not been successful to date," said Helen Collins, M.D., Senior Vice President and Chief Medical Officer of Five Prime. "We are encouraged by the preliminary data presented at SITC (Free SITC Whitepaper) 2017 and are pleased to see this trial underway."

The Phase 2 trial is expected to enroll approximately 160 patients with locally advanced or metastatic pancreatic cancer that has progressed during or after one line of chemotherapy.

About Cabiralizumab (FPA008)

Cabiralizumab is an investigational antibody that inhibits the CSF-1 receptor and has been shown in preclinical models to block the activation and survival of monocytes and macrophages. Inhibition of CSF1R in preclinical models of several cancers reduces the number of immunosuppressive tumor-associated macrophages (TAMs) in the tumor microenvironment, thereby facilitating an immune response against tumors. Cabiralizumab is currently in clinical trials in oncology indications and in pigmented villonodular synovitis (PVNS). Cabiralizumab is being developed under an exclusive worldwide license and collaboration agreement entered into with Bristol-Myers Squibb (BMS) in October 2015.

On January 25, 2018 Trovagene, Inc. (NASDAQ: TROV), a clinical-stage precision medicine biotechnology company, engaged in the development of targeted cancer therapies, reported the initiation of its Phase 2 clinical trial, evaluating the combination of PCM-075 and abiraterone acetate (Zytiga – Johnson & Johnson), in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) (Press release, Trovagene, JAN 25, 2018, View Source [SID1234523575]). This clinical trial is called UNITE, "A Phase 2 Study to Understand the Novel Combination of PCM-075 and Abiraterone and the Opportunity to Improve Treatment and Extend Response in Patients with Metastatic Castration-Resistant Prostate Cancer." The study will enroll 25 patients with mCRPC who are showing early signs of disease progression while on abiraterone/prednisone therapy and will evaluate the proportion of patients achieving disease control after 12 weeks of study treatment.

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"Initiation of the UNITE trial in mCRPC marks an important milestone in the clinical development of PCM-075 and builds upon the promising data from our completed and published Phase 1 trial in metastatic solid tumor cancers, as well as preclinical data demonstrating significant synergy for the combination of PCM-075 and abiraterone in CRPC tumor cells," said Bill Welch, Chief Executive Officer of Trovagene. "We are excited to be working with leading prostate cancer specialists and the Harvard Medical Institutions to conduct this trial and believe that the highly synergistic combination of PCM-075 and Zytiga has the potential to address the medical need to extend the benefit of response to treatment in patients with mCRPC."

Trovagene filed its Phase 2 metastatic Castration-Resistant Prostate Cancer protocol to the FDA and its active solid tumor IND in December, 2017. The Company successfully passed the 30-day FDA review period and has selected PRA Health Sciences as the Clinical Research Organization (CRO) to facilitate the trial.

About the Phase 2 mCRPC Clinical Study

In the UNITE multi-center, open-label, Phase 2 trial, the combination of PCM-075 with the standard dose of abiraterone and prednisone, all administered orally, will be evaluated to determine the proportion of patients achieving disease control after 12 weeks of study treatment. Disease control is defined by the lack of Prostate Specific Antigen (PSA) progression in patients who are showing signs of early progressive disease (rise in PSA, but minimally symptomatic or asymptomatic) while currently receiving androgen deprivation therapy (ADT) plus abiraterone and prednisone.

The Phase 2 UNITE trial will enroll 25 patients with metastatic Castration-Resistant Prostate Cancer showing signs of disease progression demonstrated by two rising PSA values separated by at least one week, while on abiraterone/prednisone therapy. The follow-up of patients will occur approximately every six weeks until disease progression in patients with stable disease, or better at the end of treatment assessments.

The Phase 2 trial also includes the following secondary observation endpoints:

The effects of PCM-075 in combination with abiraterone and prednisone on time to PSA progression in subjects with mCRPC;
The effects of PCM-075 in combination with abiraterone and prednisone on time to radiographic progression, based on the Prostate Cancer Working Group 3 (PCWG3) guidelines; and
The effects of PCM-075 in combination with abiraterone and prednisone on radiographic response (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) in subjects with mCRPC and measurable disease.
About PCM-075

PCM-075 is a highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1) enzyme, which is over-expressed in multiple hematologic and solid tumor cancers. Studies have shown that inhibition of polo-like-kinases can lead to tumor cell death, including a Phase 2 study in Acute Myeloid Leukemia (AML) where response rates up to 31% were observed when used in conjunction with a standard therapy for AML (low-dose cytarabine-LDAC) versus treatment with LDAC alone with a 13.3% response rate. A Phase 1 open-label, dose escalation safety study of PCM-075 has been completed in patients with advanced metastatic solid tumor cancers, and published in Investigational New Drugs.

PCM-075 only targets PLK1 isoform (not PLK2 or PLK3), is oral, has a 24-hour drug half-life with reversible on-target hematologic toxicities. Trovagene believes that targeting only PLK1 with reversible on-target activity and an improved dose/scheduling protocol can significantly improve on the long-term outcome observed in previous studies with a PLK inhibitor in AML.

PCM-075 has demonstrated synergy in preclinical studies with over 10 chemotherapeutic and target agents used in hematologic and solid tumor cancers, including Zytiga (abiraterone), FLT3 and HDAC inhibitors, taxanes, and cytotoxins. Trovagene believes the combination of its targeted PLK-1 inhibitor, PCM-075, with other compounds has the potential for improved clinical efficacy in Castration-Resistant Prostate Cancer (CRPC), Acute Myeloid Leukemia (AML), Non-Hodgkin Lymphoma (NHL), Triple Negative Breast Cancer (TNBC) and Adrenocortical Carcinoma (ACC).

About Castration-Resistant Prostate Cancer (CRPC)

Castration-Resistant Prostate Cancer (CRPC) is defined by disease progression despite androgen-deprivation therapy (ADT) and may present as one or any combination of a continuous rise in serum levels of prostate-specific antigen (PSA), progression of pre-existing disease, or appearance of new metastases. Prognosis is associated with several factors, including performance status, presence of bone pain, extent of disease on bone scan, and serum levels of alkaline phosphatase. Bone metastases occur in 90% of men with CPRC and can produce significant morbidity, including pain, pathologic fractures, spinal cord compression, and bone marrow failure. Paraneoplastic effects are also common, including anemia, weight loss, fatigue, hypercoagulability, and increased susceptibility to infection. Institution of treatment and the choice of systemic or local therapy depend on a number of factors.

On January 25, 2018 Advaxis, Inc. (NASDAQ:ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported that data from the investigator-initiated study evaluating the Company’s proprietary Lm-based antigen delivery product, axalimogene filolisbac (ADXS11-001), in combination with chemoradiation as a treatment for high-risk, locally advanced anal cancer were published in the International Journal of Radiation Oncology in an article titled, "Tolerability of ADXS11-001 Lm-LLO Listeria Based Immunotherapy With Mitomycin, Fluorouracil and Radiation for Anal Cancer (Press release, Advaxis, JAN 25, 2018, View Source [SID1234523562])."1 The abstract is available on-line here.

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The Phase 1 study, led by Dr. Howard Safran at Brown University, evaluated the safety and preliminary efficacy of the combination of ADXS11-001 with mitomycin, FU and intensity modulated radiation therapy in 10 patients with locally advanced, non-metastatic squamous cell anal cancer. Results showed that 9 patients achieved a complete response, and 8 patients (89%) remained disease free at a median follow-up of 42 months. One patient progressed, approximately 6 months post completion of study treatment and subsequently died from progressive disease, and one patient expired early in the study unrelated to study treatment.

Treatment-related adverse events were consistent with the observed safety profile of ADXS11-001, and consisted of mostly grade 1-2 cytokine-release related events such as chills, headache and fever. Two patients experienced grade 3 treatment-related toxicities. There were no grade 4 events and ADXS11-001 did not cause any additive chemoradiation related toxicities. All adverse events occurred within 24 hours of treatment and resolved with standard care.

These data show that ADXS11-001 can be safely administered with standard chemoradiation for patients with locally advanced, non-metastatic anal cancer.

"We are delighted to have these promising data highlighted in this prestigious, peer-reviewed journal. The complete clinical response demonstrated in patients who completed the combination treatment is very encouraging, particularly as there are limited treatment options or therapies under development for patients suffering with anal cancer," said Anthony Lombardo, interim Chief Executive Officer of Advaxis. "We look forward to advancing this promising therapy for anal cancer through investigator-led studies."