On October 30, 2017 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that new preclinical data demonstrating potent anti-tumor activity with FPT155, its novel therapeutic CD80-Fc fusion protein, were featured in a poster presentation yesterday during the 2017 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) (Press release, Five Prime Therapeutics, OCT 30, 2017, View Source [SID1234521297]). The conference is being held October 26-30, 2017, in Philadelphia. A PDF of the poster, “FPT155, a novel therapeutic CD80-Fc fusion protein, with potent anti-tumor activity in preclinical models,” will be made available on the Publications page of the Five Prime website.

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“The work done in preclinical models with FPT155 suggests that it has the potential to be a potent T cell co-stimulator with strong antitumor activity, and it may have a synergistic effect when combined with anti-PD1 therapy,” said Bryan Irving, Ph.D., Senior Vice President of Research at Five Prime. “These results are very encouraging, and we are working to complete IND-enabling studies in anticipation of an IND filing for FPT155 in mid 2018.”

Five Prime has developed FPT155, a novel CD80 (B7.1) extracellular domain (ECD)-Fc fusion protein, as a co-stimulatory molecule designed to stimulate T cell activation and break tumor immune tolerance. In vitro studies show that FPT155 induces T cell activation and cytokine production via CD28, but is dependent on co-engagement of the T cell antigen receptor, differentiating it from a CD28 “superagonist.” A murine FPT155 was generated to investigate FPT155’s impact in preclinical models and was found to be well tolerated with potent efficacy in syngeneic tumor models, including the induction of complete tumor regression in the CT26 model. mFPT155 promotes the infiltration of T cells into the tumor core and increases the ratio of effector T cells to regulatory T cells, thus inducing a favorable microenvironment for an effective antitumor immune response. Furthermore, in preclinical studies combination of mFPT155 and anti-PD1 therapy leads to stronger antitumor efficacy compared to either therapy alone.

On October 30, 2017 Heat Biologics, Inc. ("Heat") (NASDAQ: HTBX), a biopharmaceutical company developing drugs designed to activate a patient’s immune system against cancer, reported that its subsidiary, Pelican Therapeutics, Inc. ("Pelican"), received the second tranche in the amount of $6.5 million of its $15.2 million Cancer Prevention and Research Institute of Texas (CPRIT) grant award (Press release, Heat Biologics, OCT 30, 2017, View Source [SID1234521298]). To-date, Pelican has received an aggregate of $8.3 million in grants from CPRIT.

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The CPRIT award supports the pre-clinical development, manufacturing and clinical development of a 70-patient Phase 1 clinical trial for PTX-35, the company’s lead asset. PTX-35 is a novel co-stimulatory monoclonal antibody against TNFRSF25, an emerging co-stimulatory receptor on T-cells. PTX-35, in combination with checkpoint inhibitors and other immunotherapy agents, has the potential to improve clinical responses for a broad range of patients by expanding the population of antigen-specific "memory" CD8+ T-cells – the immune cells critical in tumor eradication.

"We believe these funds will enable us to progress our manufacturing efforts and advance our pipeline, with the goal of addressing the unmet need for patients who don’t respond well to current cancer therapy," said Rahul Jasuja, Ph.D., CEO of Pelican.

On October 30, 2017 NewLink Genetics Corporation (NASDAQ:NLNK) reported that indoximod, its leading drug development candidate, was granted orphan-drug designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with Stage IIb-IV melanoma (Press release, NewLink Genetics, OCT 30, 2017, View Source [SID1234521301]).

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“We are pleased to receive this orphan drug designation from the FDA,” said Charles J. Link, Jr., MD, Chairman, Chief Executive Officer and Chief Scientific Officer. “This decision supports our ongoing clinical development plans for indoximod as we continue to pursue innovative treatments for patients with cancer.”

The FDA grants orphan drug designation to investigational drugs and biologics that are intended for the treatment of rare diseases that affect fewer than 200,000 people in the U.S. Incentives may include tax credits related to clinical trial expenses, an exemption from the FDA user fee, FDA assistance in clinical trial design and potential market exclusivity for seven years following approval.

On October 30, 2017 Mateon Therapeutics, Inc. (OTCQX:MATN), a biopharmaceutical company developing investigational drugs for the treatment of orphan oncology indications, reported updated data from the fifth dose cohort of OX1222, a phase 1b dose-ranging study of OXi4503 in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) (Press release, Mateon Therapeutics, OCT 30, 2017, View Source [SID1234521300]).

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Mateon previously reported that two of four patients in this cohort of the study had morphological complete remissions following one cycle of treatment with OXi4503. A morphological complete remission occurs when an AML patient has fewer than 5% AML blasts in the bone marrow count following treatment and has no significant hematologic abnormalities or other evidence of disease.

One of the patients showing disease remission discontinued the study due to an unrelated adverse event. The other patient continued to receive treatment with an additional two cycles of OXi4503 and remains in complete remission with a cytogenetic complete response. A cytogenetic complete response occurs when testing shows eradication of chromosomal abnormalities following treatment.

"We continue to see encouraging signs of safety and efficacy for OXi4503 in Study OX1222, including complete remissions at very low doses and evidence of a dose-response as we progressively increase the dose of OXi4503 in the trial," said William D. Schwieterman, M.D., President and Chief Executive Officer of Mateon. "OXi4503 represents a completely new way to treat AML – by both killing tumor cells directly and by destroying their protective environment in the bone marrow. Based on the results seen to date, we are excited about the enormous potential for this compound in relapsed/refractory AML, especially in older patients unable to tolerate the high levels of chemotherapy typically needed to see a response. There is a huge unmet medical need in these patients and they specifically appear to benefit from treatment with OXi4503."

Summarized initial efficacy data generated to date from OX1222 in relapsed/refractory AML or MDS are as follows:

Cohort (Dose) n CR% PR% ORR%
Cohort 1 (3.75 mg/m2) 6 17% 0% 17%
Cohort 2 (4.68 mg/m2) 4 25% 0% 25%
Cohort 3 (6.25 mg/m2) 4 25% 25% 50%
Cohort 4 (7.81 mg/m2) 3 0% 33% 33%
Cohort 5 (9.76 mg/m2) 4 50% 0% 50%
n: number of patients
CR: complete remission
PR: partial remission
ORR: overall response rate (sum of partial and complete)
OXi4503 continues to have a favorable safety profile. The most common adverse events (AEs) of any grade across all cohorts include neutropenia, fever, nausea, anemia and diarrhea. Grade 3 or above AEs which were related to treatment include anemia (32%), decreased platelet count (27%), decreased neutrophil count (23%) and decreased white blood cell count (18%).

Mateon is in the process of expanding the size of future, higher-dose cohorts to 10 patients to increase the utility of the data generated. The company is also continuing discussions to secure a partner or otherwise obtain additional capital prior to initiating treatment in the sixth cohort of Study OX1222.

About Acute Myeloid Leukemia
A devastating form of cancer of the blood and bone marrow, AML is the most common type of acute leukemia in adults and accounts for the greatest number of leukemia deaths in the United States. There is no standard regimen of care for patients who relapse following front-line treatment or have refractory disease. According to the NIH’s National Cancer Institute Surveillance, Epidemiology and End Results (SEER) program, there are an estimated 21,380 new cases of AML and 10,590 deaths expected in 2017 in the United States. AML arises from a clonal hematopoietic stem cell and is characterized by accumulation of malignant myeloblasts in the bone marrow and results in ineffective hematopoiesis. AML often responds initially to front-line treatment of conventional cytotoxic chemotherapy, but it often relapses and long-term disease-free survival is low, posing a significant challenge to treat relapsed and/or refractory disease.

About OXi4503
OXi4503 has received Fast Track designation from the U.S. Food and Drug Administration for the treatment of AML. It disrupts tumor vasculature residing within bone marrow while simultaneously targeting malignant myeloid cells. Preclinical data show that OXi4503 disrupts bone marrow endothelial cells which normally protect AML cells from exposure to chemotherapeutic agents. In human xenograft animal models of AML, OXi4503 has demonstrated almost complete elimination of leukemic cells. In other animal models, the combination of OXi4503 and cytarabine has shown a much greater effect against AML than either agent alone.

On October 30, 2017 Siamab Therapeutics, Inc., a biopharmaceutical company developing novel cancer immunotherapies, reported the presentation of new preclinical data demonstrating the safety of its novel anti-Sialyl-Tn (STn) antibody drug conjugates (ADCs) in multiple animal models, including non-human primates (NHPs) (Press release, Siamab Therapeutics, OCT 30, 2017, View Source [SID1234521303]). These results add to the company’s efficacy data findings showing that its anti-STn antibody therapeutics inhibit tumor progression in cell-line-derived and patient-derived xenograft (PDX) ovarian cancer and pancreatic cancer mouse models, with complete regression observed in some treatment arms. The preclinical efficacy and safety data were presented in a poster presentation at the 2017 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), held October 26-30, 2017, in Philadelphia.

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Siamab’s platform enables the development of highly specific monoclonal antibody (mAb) therapeutics that target cancer cell surface glycans called tumor-associated carbohydrate antigens (TACAs), a novel class of cancer-specific antigens. TACAs are implicated in immune suppression, chemoresistance, and a cancer stem cell (CSC) phenotype.

“Our lead ST1 program shows compelling efficacy and safety across a range of PDX and xenograft studies, underscoring the promise of our anti-STn antibody approach to treat chemoresistant solid tumors,” said Jeff Behrens, president and chief executive officer of Siamab. “The new data from a pilot pharmacokinetic/toxicity study in primates demonstrate the favorable safety and tolerability of ST1 in large animals. The NHP results are extremely encouraging and provide an important step to de-risk IND-enabling GLP toxicity studies, which we plan to initiate in 2018.”

The poster presentation, titled “Humanized anti-Sialyl-Tn monoclonal antibody-drug conjugates (ADCs) inhibit tumor growth in vivo and in vivo,” was presented during the Therapeutic Agents: Biological poster session. In the poster, Siamab scientists and collaborators reported data demonstrating anti-tumor effect in vitro utilizing humanized anti-STn ADCs as well as inhibition of tumor progression in vivo in both cell line and PDX ovarian cancer models with complete regressions observed in some treatment groups. No significant weight loss was observed for any of the treatment groups in these models indicating the therapy was well tolerated by all the groups. In addition, the poster featured new safety data demonstrating Siamab’s anti-STn ADC has an excellent safety profile through the completion of a non-GLP pilot pharmacokinetic/toxicity study in non-human primates. Two doses were administered at days 1 and 22. Dose levels were 1mg/kg, 3mg/kg, and 6mg/kg. No weight loss or deaths occurred in the study and no gross pathology changes were observed in all organs examined. All clinical chemistry results (liver, kidney function, etc.) were normal throughout the study.

ST1, Siamab’s lead antibody program targeting STn, is in late stage preclinical development for the treatment of solid tumors. The elevated presence of STn—a key TACA observed in a number of solid tumors, including ovarian, prostate, pancreatic, gastric, and colon—is associated with metastatic disease, poor prognosis, and reduced overall survival. Elevation of STn expression is linked to chemotherapy resistance and enables tumors to evade the host immune system. Siamab has also identified the presence of STn on myeloid-derived suppressor cells (MDSCs), which are major regulators of immune response in cancer and influence the tumor microenvironment by suppressing T cells. STn is a major reported constituent of two established CSC biomarkers, CD44 and MUC1, which reside on both CSCs and mature malignant cells in some cancer types.

Siamab is utilizing STn-selective antibodies to develop both tissue- and serum-based biomarker assays with the potential to become companion diagnostics for both the stratification of patients as well as tools for assessing the pharmacodynamic action of the anti-STn therapeutic in the clinic.

Siamab recently announced it has entered into a strategic discovery collaboration with Boehringer Ingelheim with the goal of developing anti-cancer therapeutics targeting TACAs. Siamab will apply its proprietary technology platform to generate TACA-specific antibodies for use in multiple solid tumor applications. Financial terms of the agreement were not disclosed.