On October 2, 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 breast, prostate, colorectal and leukemia, reported the presentation of preclinical data demonstrating significant tumor regression with the combination of onvansertib and paclitaxel, versus either agent alone, in models of triple-negative breast cancer (TNBC) (Press release, Trovagene, OCT 2, 2019, View Source [SID1234540030]).

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The data was featured in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress on Sunday, September 29th, 2019.

"The development of new options to treat TNBC that is resistant to standard-of-care chemotherapy can address a critical unmet clinical need," said Antonio Giordano, MD, PhD, medical oncologist at Medical University of South Carolina (MUSC). "We value our collaboration with Trovagene, and we believe that our preclinical data confirms the potential therapeutic benefit of onvansertib and warrants further evaluation. Planning for the initiation of a clinical trial targeting TNBC patients with the highly-aggressive p53 mutation is currently underway at MUSC."

TNBC is an aggressive form of the disease accounting for 12 to 18% of breast cancers. Although chemotherapy can be effective as standard-of-care, many patients become resistant to treatment. The TP53 gene is mutated in approximately 80% of TNBC and the mutation is considered a target marker. TNBC is defined by the absence of estrogen and progesterone receptors and the absence of HER2 overexpression. These cancers represent a heterogeneous breast cancer subtype with a poor prognosis. Few systemic treatment options exist besides the use of chemotherapy. Currently, there are no approved targeted therapies to treat TNBC.

Presentation Highlights

Background:

Somatic mutation in TP53 gene (mutp53) is a strong prognostic marker in breast cancer
Triple negative breast cancer (TNBC) is characterized by up to 80% mutp53 and the greatest overall genomic instability among subtypes
Polo-like kinase 1 (PLK1) regulates progression of cells through the G2 phase of the cell cycle
Hypothesis that mutp53 in the context of breast cancer can predict synergy to paclitaxel plus onvansertib, an orally available highly selective PLK1 inhibitor
Significant Clinical Need for New Targeted Treatment Option (Onvansertib + Paclitaxel):

Cell lines undergo G2/M cell-cycle arrest following PLK1 (onvansertib) inhibition
Paclitaxel synergizes with onvansertib (the activity of the two drugs together is greater than that of each drug alone) and induces apoptosis (death) of cancer cells
Currently, treatment options are limited to chemotherapy and there is a significant medical need to develop a targeted therapeutic option for the treatment of breast cancer patients with TP53 mutation
A clinical study to assess the safety and preliminary efficacy of the combination of onvansertib and paclitaxel as a potential new targeted treatment option in TNBC is warranted
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 1b/2 clinical trial of onvansertib in combination with low-dose cytarabine or decitabine in patients with relapsed or refractory AML (NCT03303339). Onvansertib has been granted orphan drug designation by the FDA in the U.S. and by the EC in the European Union for the treatment of patients with AML.

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 2, 2019 Q BioMed Inc. (OTCQB: QBIO), reported that it has entered into a settlement agreement with BioNucleonics Inc. to complete the outright acquisition of the non-opioid cancer bone pain drug Strontium-89 Chloride USP (Press release, Q BioMed, OCT 2, 2019, View Source [SID1234540029]). Q BioMed will assume immediate ownership of the drug, including the aNDA (abbreviated new drug application), under a mutually favorable global royalty agreement.

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Strontium-89 is an important therapeutic option for the treatment of metastatic bone cancer pain. The drug has a long history of providing well-documented pain relief for patients suffering from the excruciating pain associated with primary cancers that have spread to the bone, including breast, prostate, lung and others. The drug is administered by a single injection and has been shown to reduce or even eliminate the need for opioid therapies. It is effective in reducing pain in the majority of patients and lasts 3 or more months with one dose.

Q BioMed has been gearing up its commercial efforts in anticipation of the successful outcome of this action as well as the pending FDA approval of the contract facility that will manufacture the drug in the US.

The Company believes that this is the ideal time to be launching the product given the current climate surrounding the over-use of opioid drugs. In addition, as more therapies come to market for the treatment of primary cancers, more people are living longer with metastatic disease. It is estimated that approximately two million patients experience debilitating bone pain from metastatic disease. The opportunity to provide improved quality of life to this group is substantial.

QBioMed CEO Denis Corin said, "We have never been more confident in the merits of this program. It has taken longer than anticipated to get here, but we are soon going to be able to serve the needs of patients suffering from metastatic bone pain and provide them the chance to minimize their pain and improve their quality of life during a meaningful moment in their lives. With millions of potential patients, this is a major market opportunity for us and our shareholders. In addition, we are investigating and planning expansion trials to provide additional indications for the drug and entry into an even larger therapeutic market."

While we cannot comment on the FDA review of our contract facility, we are proactively preparing for launch late this year. We have on-boarded our commercial team and will make further announcements regarding national and international distribution in the very near future. In addition, our commercial infrastructure is prepared, including pharmacovigilance, medical information, government contracting and marketing.

We look forward to updating our shareholders and those awaiting drug availability in the very near term.

On October 2, 2019 Nektar Therapeutics (Nasdaq: NKTR) reported the acceptance of five clinical and preclinical data abstracts for its immuno-oncology portfolio at the 2019 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Nektar Therapeutics, OCT 2, 2019, View Source [SID1234540028]). The presentations include an oral session with a presentation of updated data from the PIVOT-02 study of bempegaldesleukin (NKTR-214, bempeg) with nivolumab in patients with first-line metastatic melanoma. The 2019 SITC (Free SITC Whitepaper) Annual Meeting is being held from November 6 to November 10, 2019, at the Gaylord National Hotel & Convention Center in National Harbor, Maryland.

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Details of the oral presentation are as follows:

Abstract Title: "Clinical activity, including deepening of response, of BEMPEG plus NIVO in previously untreated patients with metastatic 1L Melanoma: results from the Phase 1/2 PIVOT-02 Study"
Abstract: O35
Presenter: Dr. Adi Diab, MD Anderson Cancer Center
Session Title: Concurrent Session 310: Combination Phase 1-2 Clinical Trials
Date: Saturday, November 9, 2019, 5:15 p.m. – 5:30 p.m. Eastern Standard Time

Details of the poster presentations are as follows:

Abstract P619: "NKTR-255, a polymer-conjugated IL-15 receptor agonist, enhances efficacy of therapeutic monoclonal antibodies with ADCC activity in solid tumor models", Kivimäe, S., et al.
Session Date and Time: Friday, November 8th from 7:00 a.m. – 8:00 p.m. Eastern Standard Time

Abstract P623: "Bempegaldesleukin in combination with local radiation and systemic checkpoint blockade induces a robust systemic anti-tumor immunity", Pieper, A., et al.
Session Date and Time: Friday, November 8th from 7:00 a.m. – 8:00 p.m. Eastern Standard Time

Abstract P622: "Characterization and comparison of NKTR-255, a polymer-conjugated IL-15 versus IL-15 superagonist", Miyazaki, T., et al.
Session Date and Time: Saturday, November 9th from 7:00 a.m. – 8:00 p.m. Eastern Standard Time

Details of the Trials in Progress poster presentation are as follows:

Abstract P387: "A Multicenter, Open-Label, Exploratory Platform Study to Evaluate Biomarkers and Immunotherapy Combinations for the Treatment of Patients with Metastatic Castration-resistant Prostate Cancer (PORTER)", Nissola, L., et al.
Session Date and Time: Friday, November 8th from 7:00 a.m. – 8:00 p.m. Eastern Standard Time

About Bempegaldesleukin (NKTR-214)
Bempegaldesleukin is designed to stimulate cancer-killing immune cells in the body by targeting CD122 receptors found on the surface of these immune cells. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these effector T cells.1 In clinical and preclinical studies, treatment with bempegaldesleukin resulted in expansion of these cells and mobilization into the tumor micro-environment.2,3

About NKTR-255
NKTR-255 is an IL-15 receptor agonist designed to engage the IL-15 pathway to stimulate and expand natural killer (NK) cells and promote the survival and expansion of central memory CD8+ T cells without inducing suppressive regulatory T cells. Through optimal engagement of the IL-15Rα/IL-2Rγ receptor complex, NKTR-255 enhances formation of long-term immunological memory which may lead to sustained anti-tumor immune response. Native rhIL-15 is rapidly cleared from the body and must be administered frequently and in high doses limiting its utility due to toxicity. NKTR-255 is designed with IL-15 receptor alpha specificity to optimize biological activity and is uniquely engineered to provide optimal exposure and an improved safety profile.

On October 2, 2019 Elicio Therapeutics, a next generation immuno-oncology company, reported that it has closed its $33 million Series B financing (Press release, Elicio Therapeutics, OCT 2, 2019, View Source [SID1234540027]). Proceeds from the financing will be used to advance Elicio’s pipeline of novel lymph node targeted immuno-therapies, including ELI-002, an Amphiphile mKRAS vaccine (AMP KRAS). ELI-002 targets all seven KRAS mutations that drive 99% of all mKRAS-driven cancers, estimated to be 25% of all human solid tumors.

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"We believe ELI-002 can become a universal mKRAS vaccine with the potential to treat and prevent disease recurrence for hundreds of thousands of patients with mKRAS-driven cancers, including pancreatic, colorectal and lung cancer," said Robert Connelly, CEO of Elicio. "This new funding is a strong endorsement of this program, the Amphiphile platform, and our progress."

Elicio has established an international investor base, including Clal Biotechnology Industries, Livzon Pharmaceutical Group and Efung Capital. "We are gratified to be able to expand our investor base and strengthen our balance sheet as we advance multiple Amphiphile immuno-therapies towards initial patient studies," Connelly said.

Elicio’s AMP KRAS vaccine ELI-002 has completed preclinical validation, IND-enabling GLP toxicology studies, GMP manufacturing, and a pre-IND meeting with the FDA and Elicio intends to begin an initial patient study in pancreatic cancer patients in the first half of 2020. These trials will be multi-site, randomized, controlled studies. Initial ELI-002 pancreatic cancer patient data is expected in the second half of 2020.

About the Amphiphile Platform
The Elicio Amphiphile platform enables precise targeting and delivery of immunogens and cell-therapy activators directly to the lymphatic system, the "brain center" of the immune response, to significantly amplify and enhance the body’s own system of defenses, defeat solid and hematologic cancers, and prevent their recurrence. Once in the lymph nodes, Amphiphile immunotherapies are taken up by antigen presenting cells (APC’s) to orchestrate signaling to natural or engineered immune cells in order to maximize therapeutic immune responses to disease. This strategy has been used to improve the activity of immunostimulatory agents, antigens, adjuvants, and cell-therapies that generate little to no response when used in the conventional forms. By precisely targeting these immunotherapies to the lymph nodes, Amphiphiles can unlock their full potential to generate and amplify anti-tumor immune responses. This substantially enhanced anti-tumor functionality and long-term protective memory may someday unlock the full potential of the immune response to eliminate cancer.

On October 2, 2019 IASO Biotherapeutics (IASO BIO), a clinical stage biotechnology company advancing the development of innovative therapies for cancer, and Innovent Biologics, Inc. (Innovent) (HKEX:01801), a world-class biopharmaceutical company that develops and commercializes high quality medicines, reported that IASO BIO has received National Medical Products Administration (NMPA) approval for an Investigational New Drug Application (IND) for CT103A—an innovative therapy for the treatment of relapsed refractory multiple myeloma (rr/mm) patients (Press release, IASO BioMed, OCT 2, 2019, View Source [SID1234540026]). IASO Bio and Innovent will start a Phase Ib/II study to confirm the R2PD and move to phase II shortly after, with approval anticipated in 2021.

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Multiple Myeloma is a deadly blood cancer that often infiltrates the bone marrow causing anemia, kidney failure, immune problems and bone fractures. With a global annual incidence rate of 2/100,000 persons, it is one of the most commonly diagnosed blood cancers, second only to non-Hodgkin lymphoma.

Hu Guang, Ph.D., Director of R&D at IASO BIO, commented that: "This is an important milestone that allows us to continue with CT103A’s clinical development for the treatment of rr/mm. We’re a young company, and this is a big step forward in achieving our objectives to develop and bring to market the most advanced therapies for treating patients more effectively."

News of the IND approval coincided with the latest presentation of CT103A clinical results at the 17th Annual International Myeloma Workshop, Boston, September 12-15 (Abstract #440).

This annual event is devoted to fostering scientific and clinical exchange on the latest breakthroughs in multiple myeloma and related plasma cell disorders.

In an IIT study conducted by Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, researchers presented compelling results for efficacy and persistence of a therapy that may provide patients, having relapsed from a prior CAR-T, an option for CAR-T retreatment.

In general, the treatment was well tolerated, with dosage levels ranging from 1X106, 3X106 and 6X106 CAR-T/kg.

CRS occurred in 17/18 patients (Grade 1&2- 66.6% (12), Grade 3- 22.2% (4), Grade 4- 5.6% (1)), but was generally manageable with no neurotoxicity.

At even the lowest dosage level (1 x106 cells/kg), CT103A remains effective with an improved safety profile. For response, 7/8 evaluable patients achieved VGPR or better. With respect to safety, only 1/8 evaluable patients experienced CRS at > grade 2.

About CT103A:

CT103A is an innovative therapy co-developed by IASO BIO and Innovent Biologics, Inc. Previous studies indicated patients with relapsed/refractory multiple myeloma (RRMM) who received high-dose BCMA-targeting CAR-T cells may achieve better remission but have worse adverse events. Moreover, once the disease progresses, the re-infusion of CAR-T cells is not effective. To solve this dilemma, CT103A has been developed, a lentiviral vector containing a CAR structure with a fully human scFv, CD8a hinger and transmembrane, 4-1BB co-stimulatory and CD3z activation domains. Based on strict selection and screening, utilizing a proprietary in-house optimization platform, the construct of the CT103A CAR-T is potent and persistent.

About Nanjing IASO Biotherapeutics:

Founded in March 2017, IASO BIO is a clinical stage biotechnology company advancing the development of innovative cell therapies for cancer. IASO BIO is dedicated to curing cancer using engineered autologous/allogenic T cell therapies designed to enhance the immune system’s ability to recognize and eradicate cancer cells.

Currently, IASO BIO is developing over 10 high-potential, high-end biopharmaceutical products, utilizing a fully-human scFv sequence targeting hematological, solid and virus associated tumors. Additional development efforts include unique TCR-like CAR-T cell therapy products for indications such as gastric cancer, nasopharyngeal carcinoma and viral infection related solid tumors.

IASO BIO has developed broad capability including; a proprietary phage library（>1×1011）supporting the development of CAR-T products, antibody drugs and intracellular targets, a screening system using high-throughput CAR-T analysis techniques and large scale data mining to obtain Best-in-class CAR-T drug candidates, in-house plasmid, lentivirus and CAR-T production technology platforms meeting the requirements for IND submissions and clinical research. For more information, please visit: www.iasobio.com