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.

On October 30, 2017 Aviragen Therapeutics, Inc. (NASDAQ:AVIR), a company focused on the discovery and development of direct-acting antivirals to treat infections that have limited therapeutic options, and Vaxart, Inc., a privately-held, clinical-stage company focused on developing oral recombinant vaccines based on its proprietary delivery platform that allows for administration by tablet rather than by injection, reported that the companies have entered into a definitive merger agreement (Press release, Aviragen Therapeutics, OCT 30, 2017, View Source [SID1234639795]). The merger will result in a combined company, Vaxart, Inc., focused on developing orally-delivered therapeutics and prophylactics to address a variety of viral infections.

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"We are thrilled with the prospect of combining forces with Aviragen, which will create a deep pipeline of antiviral products and allow Vaxart to accelerate development of the promising vaccine candidates that are based on our proprietary oral delivery platform," said Wouter Latour, M.D., Chief Executive Officer of Vaxart. "This transaction gives us the opportunity to build on the positive Phase 2 challenge study results we announced recently for our influenza oral tablet vaccine, as well as the excellent results we obtained in the safety and immunogenicity studies with our norovirus vaccine. Additionally, it will provide us access to Aviragen’s antiviral assets, including their BTA074 Phase 2 program for the treatment of condyloma caused by HPV, which is on track to complete enrollment this quarter and to report top-line safety and efficacy data in the second quarter of 2018."

"We believe our oral vaccine programs are significantly de-risked based on the positive clinical outcome of the BARDA-funded H1N1 influenza Phase 2 challenge study which serves as proof of concept for our technology platform as a whole," continued Latour, "and we look forward to taking our norovirus vaccine into a Phase 2 challenge study next. Norovirus is the leading cause of acute viral gastroenteritis in the United States, causing frequent outbreaks across the population, and we believe our oral tablet vaccine would be the optimal approach to address this unmet medical need."

The Vaxart technology platform has been engineered for the delivery of a wide range of oral vaccines, initially targeting norovirus, human papilloma virus (HPV), respiratory syncytial virus, and influenza, using a convenient and room temperature-stable tablet, which eliminates the need for injection. In clinical studies to date, Vaxart vaccines consistently generated broad systemic and local immune responses that could provide important advantages in preventing infection, as well as robust T cell responses that we believe are essential to obtain a therapeutic benefit in chronic viral infection and cancer.

"After a comprehensive review of strategic alternatives, we are delighted to announce this transaction with Vaxart, which will complement Aviragen’s focus on infectious diseases and position us to create both near and long-term value for our stockholders," said Joseph M. Patti, Ph.D., President and Chief Executive Officer of Aviragen Therapeutics. "Vaxart is well-funded to advance its norovirus and HPV antiviral vaccine programs, and together with BTA074, the combined companies are poised to provide meaningful value-creating data readouts."

Today, Vaxart will be announcing positive results from the company’s Phase 1b open-label, dose-ranging study assessing the safety and immunogenicity of VXA-G1.1-NN, Vaxart’s norovirus oral tablet vaccine, in 60 healthy adult volunteers. VXA-G1.1-NN met both the primary and secondary endpoints for safety and immunogenicity in the clinical trial. Based on the favorable clinical data, a Phase 2 norovirus challenge study is expected to begin in the second half of 2018. To date, Vaxart has dosed more than 300 adult volunteers with its vaccines for norovirus, respiratory syncytial virus and influenza.

About the Transaction

The exchange ratio in the merger agreement was determined by assigning $60 million in value to Aviragen for its financial and clinical assets and $90 million in value for Vaxart’s assets. On a pro forma basis, after giving effect to the number of shares of Aviragen common stock issued in the merger, Vaxart’s securityholders will own approximately 60% of the combined company and Aviragen securityholders will own approximately 40% of the combined company, subject to certain potential adjustments as described in the merger agreement. The transaction has been approved by the board of directors of both companies. The merger is expected to close in the first quarter of 2018, subject to the approval of the stockholders of each company as well as other customary conditions. Wouter Latour, M.D., will serve as Chief Executive Officer of the combined company.

Upon the closing of the transaction, the name of the combined company will become Vaxart, Inc. and shares of the combined are expected to continue trading on NASDAQ under the proposed ticker symbol "VXRT."

Stifel, Nicolaus & Company, Incorporated is acting as financial advisor to Aviragen, and Dechert LLP is serving as legal counsel to Aviragen. Cooley LLP is serving as legal counsel to Vaxart.

Aviragen will reduce its workforce by six to a total of 10 full-time employees, who will remain on board to complete the BTA074 Phase 2 clinical trial and assist with the transition of duties to the Vaxart management team.

Aviragen and Vaxart management will host a conference call this morning, Monday, October 30, 2017 at 8:30 a.m. EDT to discuss the planned merger. To participate in the conference call, please dial (877) 312-5422 (United States) or (253) 237-1122 (international) and refer to conference ID number 6295889. A replay of the conference call can be accessed under the Investors section of Aviragen’s website at www.aviragentherapeutics.com and on the Vaxart website at www.vaxart.com.

On October 30, 2017 Sierra Oncology, Inc. (NASDAQ: SRRA), a clinical stage drug development company focused on advancing next generation DNA Damage Response (DDR) therapeutics for the treatment of patients with cancer, reported preclinical data supporting the ongoing clinical development strategy for its Chk1 inhibitor, SRA737 (Press release, Sierra Oncology, OCT 30, 2017, View Source [SID1234521304]). The results were presented in a poster on October 29th at the 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 in Philadelphia, Pennsylvania.

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“The data generated from these experiments are consistent with recent findings from our research and demonstrate that a potent and selective Chk1 inhibitor such as SRA737 can effectively synergize with sub-therapeutic doses of gemcitabine to induce replication catastrophe and tumor cell death,” said Dr. Alan R. Eastman, Professor at the Geisel School of Medicine at Dartmouth and the founding Director of the Molecular Therapeutics Research Program of the Norris Cotton Cancer Center at Dartmouth-Hitchcock. “I look forward to results from the clinical study Sierra is conducting which translates this novel strategy for the treatment of patients with advanced cancers.”

“Chk1 is essential for managing replication stress (RS), which is intrinsically elevated in certain oncogene-transformed tumors, and can also be further enhanced by chemotherapeutic drugs like gemcitabine. While gemcitabine likely causes RS by depleting deoxynucleotide (dNTP) and damaging DNA, Chk1 protects against RS through a variety of molecular mechanisms. Consequently, tumor cells become highly reliant on Chk1 to manage replication stress and its downstream consequences in order to survive and continue to proliferate,” added Dr. Christian Hassig, Senior Vice President of Research at Sierra Oncology. “Through our research, we have demonstrated that SRA737 has the potential to synergize with several clinically important chemotherapeutic inducers of RS to kill tumor cells in vitro at low concentrations. We also demonstrated that the combination of SRA737 and gemcitabine may prove efficacious in gemcitabine-resistant clinical settings and that SRA737 can be potentiated by sub-therapeutic doses of gemcitabine in animal models of cancer.”

“Replication stress has been recognized as a potent driver of genomic instability, a fundamental hallmark of cancer, and is rapidly emerging as an area of dynamic scientific research,” stated Dr. Nick Glover, President and CEO of Sierra Oncology. “Tumors harboring high levels of intrinsic or exogenous forms of replication stress are potential candidates for therapeutic intervention using SRA737. We are actively leveraging these concepts in our ongoing monotherapy and low-dose gemcitabine combination clinical trials.”

About the Poster
Title: The Chk1 inhibitor, SRA737, demonstrates chemical synthetic lethality with replication stress-inducing agents, including novel low-dose gemcitabine, in preclinical models of cancer.
Poster #181; Abstract #B181:
The Poster is available on the company’s website at www.sierraoncology.com.

Data reported in the Poster demonstrated that:

The combination of SRA737 with a range of RS-inducing agents was highly synergistic in a panel of 15 cell lines of diverse tissue lineages, with the strongest synergy observed with gemcitabine.
Profound synergy between SRA737 and gemcitabine was observed in several bladder cancer cell lines as well as in human patient-derived bladder cancer 3D cultures, further supporting the clinical development of this RS-inducing combination.

Significant anti-tumor activity and increased survival (vs. control) were observed when SRA737 and gemcitabine were dosed in combination in a highly aggressive gemcitabine resistant bladder carcinoma PDX model. These findings suggest that the combination of SRA737 and gemcitabine may be efficacious in gemcitabine-resistant clinical settings.
Strikingly, anti-tumor activity was observed when SRA737 was combined with a sub-therapeutic dose of gemcitabine in xenograft models of colorectal adenocarcinoma and osteosarcoma. This combination was shown to increase RS markers by three to five-fold over the change noted with gemcitabine alone. These findings support i) the development of SRA737 in combination with low, sub-therapeutic doses of gemcitabine and, ii) the broader application of this unique combination in tumor indications where gemcitabine is not standard of care.

Vertex Pharmaceuticals has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Vertex Pharmaceuticals, 2017, OCT 30, 2017, View Source [SID1234521308]).

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