On December 4, 2017 Kymab’s reported that data at the British Society for Immunology Congress demonstrates efficient identification and validation of human antibodies (Press release, Kymab, DEC 4, 2017, View Source [SID1234537007])

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Three poster presentations at the 2017 British Society for Immunology Congress describe how Kymab’s efficient human antibody platforms were able to identify an anti-PD-L1 antibody, KY1003, and show it was an effective anti-tumour antibody in in vitro and in vivo models.

In Rachael Kimber’s poster, Cell based screening cascade to select anti-human PD-L1 antibodies, the team describe a cell-based, in vitro screening cascade that enabled functional characterisation of anti-human PD-L 1 antibodies.

They identified a panel of potent fully human, antagonistic antibodies that bind human and cynomolgus PD-L1 and enhance T-cell activity, identifying a lead clone, KY1003, that has the characteristics of a clinically relevant PD-L1 antibody.

Lucy Hepburn presents Development and characterization of a human T cell:tumour cell co-culture assay for assessment of immunomodulatory antibodies, which suggests that prolonged co-culture of human T-cells with the A375 tumour cell line, designed to mimic chronic antigen stimulation, generates T-cells that appear ‘exhausted’.

By using these T-cells, the team confirm that Kymab’s anti-PD-L1 antibody, KY1003, can enhance in vitro T-cell killing of A375 cells and inhibit immunosuppressive PD-1/PD-L1 signalling to increase tumour elimination by T cells in vivo.

Morgane Lecointre’s poster, Development of a "tumour-educated" T cell killing assay for predictive in vitro assessment of anti-PD-L1 antibodies, demonstrates how KY1003 can revert T-cell exhaustion in in vitro models using A375 tumour cells.

Importantly, KY1003 shows a strong anti-tumour efficacy in an in vivo human melanoma xenograft model. The approach is biologically relevant in validation of antibodies that target T-cell immune-modulatory molecules.

Notes to Editors
PDF versions of the posters
Cell based screening cascade to select anti-human PD-L1 antibodies (0.5 MB: Kimber et al., Poster P074)
Development and characterization of a human T cell:tumour cell co-culture assay for assessment of immunomodulatory antibodies (0.7 MB: Hepburn et al., Poster P077)
Development of a "tumour-educated" T cell killing assay for predictive in vitro assessment of anti-PD-L1 antibodies (4.3 MB: Lecointre et al., Poster P075)

On December 4, 2017 Propanc Biopharma Inc. (OTCQB: PPCB) ("Propanc Biopharma" or "the Company"), a clinical stage biopharmaceutical company focusing on development of new and proprietary treatments for cancer patients suffering from solid tumors such as pancreatic, ovarian and colorectal cancers, reported that the Company has made significant recent progress towards full scale Good Manufacturing Process (GMP) manufacture of its lead product, PRP, for First-In-Human studies, expected to commence in 2018 (Press release, Propanc, DEC 4, 2017, View Source [SID1234522367]). Research and development activities conducted with its European Contract Manufacturing Organization (CMO) experienced in the production of biopharmaceuticals, have been successful in developing a process capable of purifying and stabilizing the two active drug substances of the PRP formulation, trypsinogen and chymotrypsinogen, which is an important requirement during the manufacturing process. As a result, the Company is set to commence engineering runs of manufacturing the finished drug product, prior to full scale GMP manufacture of PRP for human trials. PRP is a solution for once-daily intravenous administration of a combination of two pancreatic proenzymes trypsinogen and chymotrypsinogen.

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"We are delighted with the excellent progress made with our CMO in progressing PRP to its current stage of development and we are excited about our plans to move into First-In-Human studies next year," said Dr Julian Kenyon, Propanc Biopharma’s Chief Scientific Officer. "Purifying and stabilizing each active drug substance of PRP has been technically challenging. This is due to the nature of the proenzymes which are able to auto-activate themselves, which is not unexpected for biological molecules of this nature. The work conducted by our research and development team to meet this challenge has been first class and we look forward to progressing PRP through to clinical development."

The Company expects to file its first Clinical Trial Application (CTA) for a First-In-Human study in the UK next year, initially treating late stage cancer patients with solid tumors, before progressing into two larger Phase II Proof of Concept studies in both pancreatic and ovarian cancer patients. Preclinical animal studies demonstrating proof of concept, in vivo, as well as the completion of a GLP-compliant, 28-day repeat-dose toxicology study, which helps to confirm the starting dose in humans by identifying the No Observable Adverse Effect Level (NOAEL) in an animal species, has the management team confident it has undertaken the steps necessary to achieve the best possible results in its planned human studies. This is further supported by the FDA granting Orphan Drug Designation of PRP for the treatment of one of its lead indications, pancreatic cancer, with a second application filed for ovarian cancer under evaluation.

"I am pleased with the progress of PRP and look forward to preparing our lead product for First-In-Human studies next year," said Professor Klaus Kutz, Propanc Biopharma’s Chief Medical Officer. "The Company has undertaken significant work to prepare for this important milestone, and believe the product can benefit patients suffering from aggressive solid tumors, which are most often incurable. Extending life meaningfully, but without compromising the quality of life for patients, without the side effects normally associated with standard treatment regimens, remains a high priority. We remain hopeful that PRP can become a breakthrough product for many patients worldwide."

Currently progressing towards First-In-Human studies, PRP aims to prevent tumor recurrence and metastasis from solid tumors. Eighty percent of all cancers are solid tumors and metastasis is the main cause of patient death from cancer. According to the World Health Organization, 8.2 million people died from cancer in 2012. Consequently, a report by IMS Health states innovative therapies are driving the global oncology market to meet demand, which is expected to reach $150 billion by 2020. The Company’s initial target patient populations are pancreatic, ovarian and colorectal cancers, representing an estimated combined market segment of $14 billion in 2020, according to GBI Research.

To view Propanc Biopharma’s "Mechanism of Action" video on anti-cancer product candidate, PRP, please click on the following link: View Source

To be added to Propanc Biopharma’s email distribution list, please click on the following link: View Source and submit the online request form.

On November 29, 2017, Moleculin Biotech, Inc. (the "Company") was informed that the physician-sponsored Investigational New Drug application made by MD Anderson Cancer Center for a Phase I trial of the Company’s licensed drug compound WP1066 in patients with recurrent malignant glioma and brain metastasis from melanoma has been allowed by the U.S. Food and Drug Administration (Press release, Moleculin, DEC 4, 2017, View Source [SID1234522355]).

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On December 4, 2017 Mylan N.V. (NASDAQ, TASE: MYL) and its partner, Aspen (JSE: APN), reported the U.S. launch of Myleran (busulfan) Injection, 60 mg/10 mL (6 mg/mL) Single-dose Vial, a generic version of Otsuka Pharmaceutical’s Busulfex Injection (Press release, Mylan, DEC 4, 2017, View Source [SID1234522349]). Aspen received final approval from the U.S. Food and Drug Administration (FDA) for its Abbreviated New Drug Application (ANDA) for this product, which is indicated for use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia. (1)

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As part of its partnership with Aspen, Mylan will commercialize Busulfan Injection, 60 mg/10 mL (6 mg/mL) Single-dose Vial in the U.S. Mylan has one of the largest injectable portfolios in the industry and is also one of the largest suppliers of cancer medicines by volume in the U.S.

U.S. sales for Busulfan Injection, 60 mg/10 mL (6 mg/mL) Single-dose Vial were approximately $97 million for the 12 months ending Sept. 30, 2017, according to IQVIA.

On December 4, 2017 Loxo Oncology, Inc. (Nasdaq:LOXO), a biopharmaceutical company innovating the development of highly selective medicines for patients with genetically defined cancers, reported updated clinical data from the larotrectinib pediatric Phase 1 SCOUT clinical trial (Press release, Loxo Oncology, DEC 4, 2017, View Source [SID1234522348]). These data are being presented today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Special Conference on Pediatric Cancer Research in Atlanta.

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"Targeted therapy success stories in pediatric oncology are uncommon, and larotrectinib has invigorated the pediatric oncology community," said Brian Turpin, D.O., the presenting SCOUT principal investigator and assistant professor in the division of oncology at Cincinnati Children’s Hospital. "Larotrectinib’s near universal response rate and compelling durability of response in pediatric patients with TRK fusion cancers is likely to be practice changing. Furthermore, the first-ever TRK inhibitor response in a TRK fusion glioblastoma patient highlights the potential for larotrectinib in TRK fusion central nervous system tumors."

"We are grateful to the children and families who have enabled the development of larotrectinib through their participation in clinical trials," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology.

As of a July 17, 2017 data cut-off date, 24 pediatric patients were enrolled in the dose escalation portion of the Phase 1 trial, including 17 patients with TRK fusion cancers. TRK fusion patients carried primary diagnoses of infantile fibrosarcoma, thyroid cancer, and various soft tissue sarcomas.

TRK Fusion Patients (n=17)* Patients without TRK Fusions (n=7)
Independent Review Committee Assessed Response Investigator Assessed Response Investigator Assessed Response
Overall Response Rate
(ORR = PR+CR) 93%
(95% CI: 68% – 100%) 93%
(95% CI: 68% – 100%) 0%
Partial Response (PR) 80% 67%** 0%
Complete Response (CR) 13% 27% 0%
Stable Disease 7% 7% 0%
Progressive Disease 0% 0% 100%
* 2 patients not evaluable due to having non-measurable disease at baseline.
** Includes 2 patients with unconfirmed partial responses as of July 17, 2017, which were subsequently confirmed.

Among the 17 patients with TRK fusion cancers, 94% either remain on drug or received surgery with curative intent; four patients have been followed greater than one year and 12 have been followed greater than six months.

The larotrectinib adverse event profile is consistent with data previously presented publicly. The most common treatment-related adverse events at the Phase 2 dose included increased liver function tests, neutropenia, and nausea, all largely grade 1.

These data are being presented in a poster session on December 4, 2017 and an oral presentation on December 5, 2017. The poster and presentation will be available online at View Source at the time of their scheduled presentations.

About Larotrectinib (LOXO-101)
Larotrectinib is a potent, oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRKs). Growing research suggests that the NTRK genes, which encode for TRKs, can become abnormally fused to other genes, resulting in growth signals that can lead to cancer in many sites of the body. In an analysis of 55 RECIST-evaluable TRK fusion adult and pediatric patients, larotrectinib demonstrated a 75 percent independently-reviewed confirmed overall response rate (ORR) and an 80 percent investigator-assessed confirmed ORR, across many different types of solid tumors. Larotrectinib has been granted Breakthrough Therapy Designation Rare Pediatric Disease Designation and Orphan Drug Designation by the U.S. FDA. For additional information about the larotrectinib clinical trials, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient Clinical Trial Hotline at 1-855-NTRK-123 or visit www.loxooncologytrials.com.

In November 2017, Loxo Oncology and Bayer entered into an exclusive global collaboration for the development and commercialization of larotrectinib and LOXO-195, a next-generation TRK inhibitor. Loxo Oncology leads worldwide development and U.S. regulatory activities. Bayer leads ex-U.S. regulatory activities and worldwide commercial activities. In the U.S., Loxo Oncology and Bayer will co-promote the products.

About TRK Fusion Cancer
TRK fusions are chromosomal abnormalities that occur when one of the NTRK genes (NTRK1, NTRK2, NTRK3) becomes abnormally connected to another, unrelated gene (e.g. ETV6, LMNA, TPM3). This abnormality results in uncontrolled TRK signaling that can lead to cancer. TRK fusions occur rarely but broadly in various adult and pediatric solid tumors, including appendiceal cancer, breast cancer, cholangiocarcinoma, colorectal cancer, GIST, infantile fibrosarcoma, lung cancer, mammary analogue secretory carcinoma of the salivary gland, melanoma, pancreatic cancer, thyroid cancer, and various sarcomas. TRK fusions can be identified through various diagnostic tests, including targeted next-generation sequencing (NGS), immunohistochemistry (IHC), polymerase chain reaction (PCR), and fluorescent in situ hybridization (FISH). For more information, please visit www.TRKtesting.com.