On October 22, 2019 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported the expansion of Annamycin production commitments in response to management’s assessment of positive AML clinical trial activity and the potential expansion of indications for use to include lung-localized tumors (Press release, Moleculin, OCT 22, 2019, View Source [SID1234542408]). The purchase commitment arranged through Davos Pharmaceuticals includes moving final production of Annamycin to a larger-scale suite within BSP Pharmaceuticals S.p.A. ("BSP") in Latina, Italy. Until now, BSP has been producing the clinical supplies of Annamycin in a smaller pilot-scale suite.

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Moleculin Biotech, Inc. is a clinical stage pharmaceutical company focused on the development of a broad portfolio of oncology drug candidates for the treatment of highly resistant tumors.

"Our clinical trials of Annamycin in relapsed and refractory acute myeloid leukemia ("AML") have been going better than expected, as it now appears we will be able to reach a higher maximum tolerable dose than what was established in previous clinical trials," commented Walter Klemp, Moleculin’s Chairman and CEO. "That not only increases our chances for improved patient outcomes, it places a higher demand on drug supply. Coupled with the recent discovery in animal models that Annamycin may be well suited to treat lung-localized tumors because of its ability in such models to accumulate in the lungs at nearly 6 times the level of the current standard of care anthracycline, we are clearly going to need more drug."

Dr. Donald Picker, Moleculin’s Chief Science Officer added: "With management’s view of success in clinic and the expectation of wider demand resulting from additional clinical trials in lung-localized tumors, it’s time for Moleculin to start preparing for an eventual drug approval process. That requires the development and validation of commercial scale methods and this move with BSP marks the beginning of that process. In addition to increasing the scale of clinical supply production, we will be working with BSP and with our manufacturer of API to develop the commercial scale synthesis and drug production methods we will need to ultimately prepare for New Drug Approval."

On October 22, 2019 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for multiple cancer indications, reported that the U.S. Food and Drug Administration (FDA) has approved Fast Track Designation for bemcentinib for the treatment of elderly patients with acute myeloid leukaemia (AML) whose disease has relapsed (Press release, BerGenBio, OCT 22, 2019, View Source [SID1234542424]). There are currently no marketed drugs specifically approved for all relapsed AML patients, representing a significant unmet medical need. BerGenBio has ongoing phase 2 trials in this indication and plans to seek regulatory advice from the FDA and European Medicines Agency (EMA) to determine the optimal regulatory path for bemcentinib in relapsed AML.

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Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions. Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially better than available therapy. A drug that receives Fast Track designation is eligible for the following:

More frequent meetings with FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval
More frequent communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA
Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "We are thrilled that bemcentinib has been granted Fast Track Designation. Not only does this make us eligible for accelerated approval and priority review, but it serves as an important validation of bemcentinib in this significant unmet medical need we are trying to address. Currently, bemcentinib is in expanded Phase II trials in the U.S. and Europe for the treatment of AML and the Company has recently announced positive interim top line data."

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases. In cancer, AXL suppresses the body’s immune response to tumours and drives cancer treatment failure across many indications. AXL inhibitors, therefore, have potential high value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases.

About bemcentinib

Bemcentinib (formerly known as BGB324), is a potentially first-in-class selective AXL inhibitor in a broad phase II clinical development programme. Ongoing clinical trials are investigating bemcentinib in multiple solid and haematological tumours, as monotherapy and in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy). Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity. Increase in AXL function has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers.

About AML

Acute myeloid leukemia (AML) is the most common type of aggressive leukemia in adults, which has the lowest survival rate for all types of leukemia. In 2018, it is estimated there will be nearly 20,000 new cases of AML diagnosed in the United States. Many AML patients older than age 60 are unable to tolerate intensive induction chemotherapy treatment.

On October 22, 2019 Nurix Therapeutics, Inc., a company developing therapies that control disease-causing proteins, reported that it will present data on its wholly-owned, CBL-B small molecule drug development program at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 34th Annual Meeting (SITC 2019) (Press release, Nurix Therapeutics, OCT 22, 2019, View Source [SID1234542409]). SITC (Free SITC Whitepaper) is being held on November 6-10, 2019 at the Gaylord National Hotel and Convention Center in National Harbor, Maryland.

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Presentation Details:
Title: Pharmacological evaluation of the ubiquitin ligase CBL-B as a small molecule, tumor immunotherapy target
Poster #: P669
Date: Friday, November 8, 2019
Time: 7:00 a.m. – 8:00 p.m. EST

On October 22, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage, Precision Cancer Medicine oncology therapeutics company developing drugs that target cell division (mitosis) for the treatment of various cancers including prostate, colorectal and leukemia, reported data demonstrating positive response to treatment in patients enrolled in its Phase 1b/2 trial of onvansertib in combination with FOLFIRI and Avastin (bevacizumab) for second-line treatment of KRAS-mutated metastatic colorectal cancer (mCRC) (Press release, Trovagene, OCT 22, 2019, View Source [SID1234542425]). Decreases in tumor KRAS mutational burden in response to treatment was observed in all four patients who completed their first cycle of therapy with the combination regimen, as measured by quantitative analysis of circulating tumor DNA (ctDNA).

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Colorectal cancer (CRC) is the second leading cause of cancer mortality in the U.S. Despite significant progress in the treatment of mCRC, the majority of patients succumb to the disease. Therefore, improving the effectiveness of treatments is critical to changing the outcomes for this patient population. Approximately 50% of mCRC patients have the KRAS mutation. The efficacy of current second-line therapy in terms of survival prolongation and response remains very limited, especially in this population, where there is only a 5% response rate.

"We are pleased by the early indication of response to treatment with the addition of onvansertib to standard-of care in patients with KRAS-mutated mCRC," said Dr. Thomas Adams, Chief Executive Officer and Chairman of Trovagene. "We believe the combination of onvansertib and FOLFIRI/bevacizumab has the potential to provide a much-needed safe and effective new treatment option for the approximately 50% of patients with KRAS-mutated mCRC."

"Although still early in the trial, we are encouraged by the decreases in KRAS, assessed following initial dosing with onvansertib in combination with FOLFIRI/ bevacizumab, in patients treated in the first cohort," said lead investigator Dr. Afsaneh Barzi, associate professor of clinical medicine at Keck School of Medicine of USC and medical oncologist at USC Norris Comprehensive Cancer Center. "Additionally, these patients have continued on treatment beyond the cycle 1 safety assessment, indicating that the regimen appears to be safe and well tolerated. These initial findings suggest that onvansertib may provide clinical benefit for mCRC patients who have limited therapeutic options and a poor prognosis."

An overview of the mCRC Phase 1b/2 clinical trial (NCT03829410) was also featured in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress in September 2019. The presentation included the supportive preclinical data, demonstrating synergy with the combination of onvansertib and irinotecan, a key component of the FOLFIRI regimen.

About the Phase 1b/2 Clinical Trial of Onvansertib in mCRC

The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second‑Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation (NCT03829410), will evaluate the safety and efficacy of onvansertib in combination with standard-of-care FOLFIRI and Avastin (bevacizumab). Up to 44 patients, with a confirmed KRAS mutation, metastatic and unresectable disease, who have failed or are intolerant of treatment with FOLFOX (fluoropyrimidine and oxaliplatin) with or without Avastin (bevacizumab), will be enrolled. The trial is being conducted at two prestigious cancer centers: USC Norris Comprehensive Cancer Center and The Mayo Clinic Arizona.

About Onvansertib

Onvansertib is a first-in-class, third-generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK1) enzyme, which is over-expressed in multiple cancers including leukemias, lymphomas and solid tumors. Onvansertib targets the PLK1 isoform only (not PLK2 or PLK3), is orally administered and has a 24-hour half-life with only mild-to-moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.

Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including irinotecan, FLT3 and HDAC inhibitors, taxanes and cytotoxins. Trovagene believes the combination of onvansertib with other compounds has the potential to improve clinical efficacy in acute myeloid leukemia (AML), metastatic castration-resistant prostate cancer (mCRPC), non-Hodgkin lymphoma (NHL), colorectal cancer and triple-negative breast cancer (TNBC), as well as other types of cancer.

Trovagene has three ongoing clinical trials of onvansertib: A Phase 2 trial of onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with mCRPC who are showing signs of early progressive disease (rise in PSA but minimally symptomatic or asymptomatic) while currently receiving Zytiga (NCT03414034); a Phase 1b/2 Study of onvansertib in combination with FOLFIRI and Avastin for second-line treatment in patients with mCRC with a KRAS mutation (NCT03829410); and a Phase 2 clinical trial of onvansertib in combination with decitabine in patients with relapsed or refractory AML (NCT03303339).

Trovagene licensed onvansertib (also known as NMS-1286937 and PCM-075) from Nerviano Medical Sciences (NMS), the largest oncology-focused research and development company in Italy, and a leader in protein kinase drug development. NMS has an excellent track record of licensing innovative drugs to pharma/biotech companies, including Array (recently acquired by Pfizer), Ignyta (acquired by Roche) and Genentech.

On October 22, 2019 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), currently developing pelareorep, an intravenously delivered immuno-oncolytic virus, and PrECOG LLC, a leading cancer research network, reported their collaboration in which PrECOG will run the BRACELET-1 (PrE0113) study (Press release, Oncolytics Biotech, OCT 22, 2019, View Source [SID1234542410]). The principal investigator will be Kathy Miller, MD, Ballve-Lantero Professor of Oncology at Indiana University School of Medicine and Associate Director of Clinical Research at Indiana University Melvin and Bren Simon Cancer Center, and PrECOG member. The study will take place in 15 centers in the United States and will evaluate the ability of pelareorep to make tumors immunologically visible to checkpoint inhibitors.

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"We’re very excited to be working with PrECOG on the BRACELET-1 study focused on hormone receptor-positive metastatic breast cancer patients, our target patient population," said Rita Laeufle, Chief Medical Officer at Oncolytics Biotech. "Our goal in this study is to confirm our biomarker of T cell clonality in order to predictively and prognostically select patients for the phase three study, as well as to demonstrate that pelareorep sensitizes the tumor to immunotherapy and improves clinical outcomes. By creating an immunogenic tumor environment with pelareorep, we can potentially increase the efficacy of checkpoint blockade and treat more patients with this novel treatment combination. This important study, along with our ongoing AWARE-1 trial, will help determine the design of the phase three registrational program for pelareorep in metastatic breast cancer, which we expect may involve combination therapy with a checkpoint inhibitor."

"We in PrECOG are excited to be investigating this novel approach to breast cancer treatment, and to bring cutting edge options to our patients," said Peter O’ Dwyer, MD, Chief Executive Officer, PrECOG, and Co-Chair, ECOG-ACRIN Cancer Research Group. "Approaches to increase the activity of these immunologically active agents are a focus of our research and studies like this have the potential to be relevant to these mechanisms across many tumor types."

PrECOG has multiple trials in the immuno-oncology space. "Immunotherapy remains in its infancy in the treatment of breast cancer. The potential for pelareorep to extend the benefits of immunotherapy to patients with hormone-sensitive disease could be a real advantage for patients," said Dr. Miller.

The BRACELET-1 (PrE0113) study seeks to replicate a previous trial that supported an advantage in overall survival through the use of pelareorep in patients with hormone receptor-positive (HR+) metastatic breast cancer. It is being designed as a phase 2, three-arm, 48-patient open-label study for second-line treatment in these patients. The first arm will be paclitaxel alone, the second arm will be paclitaxel plus pelareorep, and the third arm will be paclitaxel plus pelareorep, plus the PD-L1 checkpoint inhibitor, avelumab.

The design is expected to be finalized in the coming weeks with input from Oncolytics’ co-development partners Pfizer and Merck KGaA. It will then go to the FDA for review. The study is anticipated to begin enrollment in Q1 2020.

About Pelareorep
Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.

About PrECOG
PrECOG, LLC is a cancer research group formed as a not-for-profit limited liability company in 2006 by the ECOG Research and Education Foundation, Inc. A central focus of PrECOG is to support the overall purpose of the ECOG-ACRIN Cancer Research Group. Its goal is to achieve research advances in all aspects of cancer care, reduce the burden of cancer, and improve the quality of life and survival in patients with cancer. PrECOG’s current portfolio includes exploratory phase 1 and 2 studies as well as phase 3 registration studies conducted in the US and the EU. For further information, please visit www.precogllc.org and www.ecog-acrin.org.