On December 12, 2017 Innovation Pharmaceuticals, (OTCQB:IPIX) ("the Company"), a clinical stage biopharmaceutical company, reported that the European Patent Office has granted a European patent for Brilacidin, the Company’s first-in-class defensin-mimetic, in the prevention and control of Oral Mucositis (OM) (Press release, Innovation Pharmaceuticals, DEC 12, 2017, View Source [SID1234522572]). Brilacidin-OM is being developed under an FDA Fast Track designation for this indication.

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The European patent supplements other Brilacidin-OM patents that have been granted in the United States, Asia (Japan, Taiwan, China), Oceania (Australia) and South Africa. All currently issued patents have an expiration date of 2032. Additional Brilacidin-OM patent applications are pending in other key markets including Russia and South Korea.

The European patent is part and parcel to the Company’s strategy to develop and commercialize Brilacidin-OM internationally through licensing agreements. An estimated 700,000 (source: GLOBOCAN) Head and Neck Cancer (HNC) patients worldwide will develop OM this year, with the figures expected to climb to over one million annually by 2023. In spite of OM incidence rates ranging as high as 100 percent in HNC, there currently are no FDA-approved drugs for the prevention and treatment of OM in these types of cancer patients receiving chemoradiation.

"We are looking at a global product opportunity with OM that is extremely attractive and intellectual property protection is critical. With no approved drugs for our initial target indication in preventing OM in HNC, the first company to commercialize a safe and effective drug would undoubtedly command a significant portion of the market, which is estimated to be at least $1 billion worldwide," said Leo Ehrlich, Chief Executive Officer at Innovation Pharmaceuticals.

"The topline data released yesterday from our Phase 2 trial showed a meaningful reduction in the incidence of severe OM even compared to a rate somewhat lower than historic norms in the placebo arm, demonstrating Brilacidin-OM’s clear effect in preventing this extremely painful, and at times even deadly, consequence of chemoradiation in a majority of HNC patients treated with the drug. I can’t imagine a physician not wanting to prescribe, and a patient not wanting to use, a simple oral rinse like Brilacidin-OM if it would mean cutting the chance of developing severe OM by as much as 38.7 percent, as observed in patients who adhered to the requirements of the trial protocol," Mr. Ehrlich continued.

"Given the positive topline data, the Company is compelled to aggressively seek a development path that will most efficiently bring Brilacidin-OM to patients in need," said Arthur P. Bertolino, MD, PhD, MBA, President and Chief Medical Officer at Innovation Pharmaceuticals. "We intend to work diligently with the FDA and other health authorities, on a worldwide basis, and ideally in collaboration with interested potential partners, to achieve this goal. We have a potential "game changer" asset with Brilacidin-OM, able to make a big impact on a cancer patient’s well-being, and we are in the privileged position of planning wholeheartedly for the next stage of development as we strive to be the first to fill a wide void in oncology as quickly as possible."

On December 12, 2017 Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing tumor-targeted and immuno-oncology therapies based on its pioneering research in cancer epigenetics, reported that the first patient has been dosed in its Phase 1b/2 PROSTAR study of CPI-1205, a small-molecule inhibitor of EZH2, combined with enzalutamide or abiraterone/prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, Constellation Pharmaceuticals, DEC 12, 2017, View Source [SID1234522670]).

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"The initiation of this combination study marks a significant milestone for the company as we execute on our goal to rapidly advance our pipeline of epigenetic therapeutics that have the potential to address difficult-to-treat cancers," said Adrian Senderowicz, M.D., senior vice president and chief medical officer of Constellation Pharmaceuticals. "Today’s announcement marks the first evaluation of CPI-1205 in solid tumors. We anticipate advancing CPI-1205 and other therapies from our EZH2 portfolio in additional solid tumor clinical trials in the future."

CPI-1205 is a potent, highly selective, first-generation small-molecule inhibitor of EZH2, a clinically-validated target in cancer. In multiple types of cancer, including mCRPC, EZH2 contributes to drug resistance over time by enhancing pro-tumor pathways, such as androgen receptor signaling. CPI-1205 has shown single-agent activity and synergistic activity with small-molecule androgen inhibitors in preclinical studies. CPI-1205 has also demonstrated single-agent clinical activity and a dose-dependent increase in exposure correlated to pharmacodynamic biomarkers during a clinical trial of CPI-1205 in selected lymphoma patients.

"There is a tremendous need for new, safe and effective medicines for advanced prostate cancer, especially for men with progressive mCRPC," said Mary-Ellen Taplin, M.D., Dana-Farber Cancer Institute and an investigator in the trial. "We look forward to learning how CPI-1205 may help overcome resistance mechanisms in mCRPC and extend response to therapy."

The Phase 1b portion of the PROSTAR study is designed to assess safety, pharmacokinetics, pharmacodynamics, as well as a recommended Phase 2 dose (RP2D) of CPI-1205 in combination with either enzalutamide (marketed as Xtandi by Astellas and Pfizer) or abiraterone acetate (marketed as Zytiga by Janssen), which are FDA-approved second-generation androgen inhibitors. The Phase 2 portion of the PROSTAR study will assess clinical activity and potential biomarkers to identify patient populations with higher clinical anti-tumor activity to CPI-1205.

About mCRPC

mCRPC is an advanced form of prostate cancer and is defined by disease progression despite treatment with androgen depletion therapy (ADT). mCRPC may present as one, or any combination of, a continuous rise in serum levels of prostate-specific antigen (PSA), progression of known metastases, or appearance of new metastases. Prognosis is associated with several factors, including the ability to perform certain daily activities and the presence of bone pain. Additional symptoms commonly include anemia (low healthy red blood cell levels), weight loss, fatigue, hypercoagulability (abnormal blood coagulation) and increased susceptibility to infection. mCRPC presents as a spectrum of disease ranging from patients without symptoms but rising PSA levels despite ADT, to patients with metastases and significant debilitation.

About CPI-1205

CPI-1205 is a therapeutic candidate from Constellation Pharmaceuticals’ EZH2 portfolio and is an inhibitor of Enhancer of Zeste Homolog 2 (EZH2). The function of EZH2 is to selectively suppress gene expression of several pro-cancer pathways that contribute to drug resistance.

On December 12, 2017 Palleon Pharmaceuticals, a company focused on developing Glycoimmune Checkpoint Inhibitors to treat cancer, reported an agreement with King’s College London to license intellectual property developed in the laboratory of Joy Burchell, Ph.D., Professor of Glyco-Oncology at the university. This agreement gives Palleon the exclusive rights to a patent portfolio that will facilitate the development of drugs that target Glycoimmune Checkpoints, a novel approach to overcoming resistance to first-generation immuno-oncology drugs.

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Professor Burchell has been a leader in the field of aberrant glycosylation in breast cancer for over 25 years. Earlier in her career she developed tools that demonstrated that more than 90% of breast cancers, and many other carcinomas, carry glycans that are different from those carried by proteins on normal cells. She was the first to show that a mucin known as MUC1 is present in the sera of breast cancer patients. This discovery enabled the development of the CA15.3 test, a serum assay used to measure the response to breast cancer treatment and to monitor recurrence of breast cancer. More recently, Professor Burchell has been investigating how aberrant glycosylation of MUC1 plays a significant role in immunosuppression and allows the cancer to thrive.

Jim Broderick, M.D., Chief Executive Officer and Founder of Palleon, commented, "Professor Burchell’s research is at the forefront of understanding how tumors use glycans to evade the immune system. We now know that tumor cells down-regulate a wide spectrum of immune cell types by cloaking themselves in certain glycan patterns, and that this mechanism of immunosuppression can be targeted by a new class of drugs. This licensing agreement strengthens Palleon’s position as the leader in this new approach to defeating cancer’s suppression of the human immune system."

Dr. Burchell added, "We have known about the alteration of glycans on the surface of malignant cells for decades. However, recent discoveries in the field of glycoscience have demonstrated the role of glycans in immunosuppression. Glycobiology is now emerging as a major axis of immunosuppression in cancer. We expect these findings to provide the foundation for developing immuno-oncology drugs that will have a significant impact on the lives of patients."

On December 12, 2017 Immutep Limited (ASX: IMM; NASDAQ: IMMP) (Immutep or the Company), reported update on the Company’s two ongoing clinical trials with eftilagimod alpha (LAG-3Ig or IMP321). Immutep is pleased to advise that clinical studies of eftilagimod alpha are progressing well (Press release, Prima Biomed, DEC 12, 2017, View Source [SID1234522623]).
In line with previous guidance, the third cohort of TACTI-mel (Two ACTive Immunotherapeutics in melanoma), the Company’s Australian melanoma clinical trial, has now been fully recruited. The sixth and last patient of that cohort received their first treatment yesterday, bringing the total number of patients recruited for the trial to 18.

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The patients eligible to participate in the TACTI-mel Phase 1 clinical trial are those with unresectable or metastatic melanoma who have either had a suboptimal response or had disease progression with pembrolizumab (KEYTRUDA) monotherapy as a first-line of treatment. These patients are dosed with eftilagimod alpha in combination with pembrolizumab. To date, no dose limiting toxicity has been observed in any patient at any dose level. Data shows the combination to be safe and well tolerated. Data from all three cohorts is expected in H1 2018.

AIPAC (Active Immunotherapy PAClitaxel), the Company’s European clinical trial started recruitment of the randomized part of the study in January 2017. In addition to centres in Belgium and the Netherlands, competent authorities’ approvals have been received and patient recruitment has also now commenced in Poland, Hungary, United Kingdom and Germany, with France following in due course. In total, 29 out of 34 clinical sites have been activated with the outstanding site activations expected to occur in early 2018. The study is expected to be fully recruited by mid-2018.

As announced earlier in June, data from the open-label safety run-in cohort of 15 patients, who received 6mg and 30mg doses of eftilagimod alpha in combination with paclitaxel, were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL, USA. Final results received in December 2017 confirm the data presented at ASCO (Free ASCO Whitepaper). Data shows that the combination of eftilagimod alpha plus weekly paclitaxel in patients with metastatic breast cancer is safe and well tolerated, leading to an overall response rate of 47% in the safety run-in. Pharmacodynamic parameters on primary and secondary target cells confirmed the proof of principle in patients.

Eftilagimod alpha Partnering Update
Immutep’s Chinese partner for eftilagimod alpha, EOC Pharma, an oncology focused affiliate of Eddingpharm, applied in the first quarter of 2017 for an Investigational New Drug (IND) in China, in preparation before starting clinical trials. Recent positive changes in the Chinese regulatory environment are likely to speed up development of eftilagimod alpha in China.

CYTLIMIC, the Japanese NEC spin off with which Immutep has a collaboration agreement, presented a poster at ASCO (Free ASCO Whitepaper) (View Source) which showed the results of their T-cell based therapeutic cancer vaccine with eftilagimod alpha as a vaccine adjuvant. A new material transfer agreement with CYTLIMIC regarding their purchase of additional vials of eftilagimod alpha from Immutep was concluded in September 2017.

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IMP761 Update
IMP761 is the first humanized antibody which acts as an agonist to one of the three immune checkpoint molecules targeted in oncology, namely CTLA-4, PD-1 and LAG-3. Consequently, Immutep is the first company to translate the vast amount of clinical data and biologic knowledge from oncology to the field of auto-immune diseases. The preclinical development of our agonist anti-LAG-3 antibody has now been successfully advanced following an extensive cross-reactivity study on a series of 30 FDA-approved human tissues sections, a prerequisite before entering the clinic.

On December 12, 2017 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and Puma Biotechnology, Inc. (Nasdaq: PBYI) reported a preclinical research collaboration with Memorial Sloan Kettering Cancer Center (MSK) to explore the combination of Daiichi Sankyo’s investigational antibody drug conjugate DS-8201 and Puma Biotechnology’s irreversible pan-HER tyrosine kinase inhibitor neratinib (NERLYNX) in HER2-mutated or HER2-positive solid tumors (Press release, Puma Biotechnology, DEC 12, 2017, http://investor.pumabiotechnology.com/press-release/daiichi-sankyo-and-puma-biotechnology-announce-research-collaboration-major-cancer-cen [SID1234522597]).

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A team of scientists led by Maurizio Scaltriti, PhD, and in collaboration with a team of clinical investigators led by Bob Li, MD, will use isogenic models and established patient-derived xenograft models to assess the susceptibility of HER2-mutated or HER2-positive cancers to DS-8201, neratinib and other HER2-targeting therapies, elucidate mechanisms of action and resistance of these various tumor types, and evaluate the potential for synergistic combinations. Daiichi Sankyo and Puma Biotechnology will co-sponsor the research.

"Since early clinical data suggest that DS-8201 may have activity beyond breast and gastric cancers, the archetype HER2-driven tumors, we are interested in studying this asset on a molecular level as well as in combination with other HER2-targeting agents," said Tom Held, Vice President, Global Head, Antibody Drug Conjugate Task Force, Daiichi Sankyo. "In this collaboration, we are examining whether combining DS-8201 and neratinib, with its specific covalent binding to the HER2 receptor and associated increased internalization, is a rational combination therapy strategy to pursue. We are excited to join forces with Memorial Sloan Kettering and Puma to advance the understanding of combining HER2-targeted therapies to potentially treat various forms of HER2-mutated cancer."

"We are pleased to enter into this research collaboration with Memorial Sloan Kettering and Daiichi Sankyo to explore the combination of neratinib and DS-8201," said Alan Auerbach, Puma’s Chief Executive Officer and President. "Combination therapy with agents that address different and complementary pathways, with neratinib targeting the HER2 kinase and DS-8201 providing an innovative targeted delivery of a potent cytotoxic, represents an intriguing approach to the treatment of HER2 mutated tumors and helps to maximize the potential for both agents in treating cancers with a HER2 mutation."

About DS-8201

DS-8201 is the lead product in the ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, DS-8201 is a smart chemotherapy comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

DS-8201 is currently in phase 2 clinical development for HER2-positive unresectable and/or metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01), phase 2 development for HER2-positive advanced gastric resistent or refractory to trastuzumab (DESTINY-Gastric01) and phase 1 development for other HER2-expressing advanced/unresectable or metastatic solid tumors.

DS-8201 has been granted Breakthrough Therapy designation for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). DS-8201 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About NERLYNX (neratinib)

Neratinib was approved by the FDA in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX (neratinib) tablets.

Important Safety Information (ISI)
NERLYNX (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early-stage HER2 overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

Diarrhea: Aggressively manage diarrhea occurring despite recommended prophylaxis with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe and/or persistent diarrhea. Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade ≥ 2 diarrhea that occurs after maximal dose reduction.
Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. Withhold NERLYNX in patients experiencing Grade 3 liver abnormalities and permanently discontinue NERLYNX in patients experiencing Grade 4 liver abnormalities.
Embryo-Fetal Toxicity: NERLYNX can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
ADVERSE REACTIONS: The most common adverse reactions (≥ 5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased and urinary tract infection.

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) and www.NERLYNX.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

DRUG INTERACTIONS:

Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors (PPI) and H2-receptor antagonists. Separate NERLYNX by 3 hours after antacid dosing.
Strong or moderate CYP3A4 inhibitors: Avoid concomitant use.
Strong or moderate CYP3A4 inducers: Avoid concomitant use.
P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow therapeutic agents that are P-gp substrates when used concomitantly with NERLYNX.
USE IN SPECIFIC POPULATIONS:

Lactation: Advise women not to breastfeed.
Please see Full Prescribing Information for additional safety information.

The recommended dose of NERLYNX is 240 mg (six 40 mg tablets) given orally once daily with food, continuously for one year. Antidiarrheal prophylaxis should be initiated with the first dose of NERLYNX and continued during the first 2 months (56 days) of treatment and as needed thereafter.

To help ensure patients have access to NERLYNX, Puma has implemented the Puma Patient Lynx support program to assist patients and healthcare providers with reimbursement support and referrals to resources that can help with financial assistance. More information on the Puma Patient Lynx program can be found at www.NERLYNX.com or 1-855-816-5421.

About Puma Biotechnology

Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialization of innovative products to enhance cancer care. Puma in-licenses the global development and commercialization rights to three drug candidates — PB272 (neratinib (oral)), PB272 (neratinib (intravenous)) and PB357. NERLYNX (neratinib) is approved for commercial use by prescription in the United States as extended adjuvant therapy for early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy and is marketed as NERLYNX. Neratinib is a potent irreversible tyrosine kinase inhibitor that blocks signal transduction through the epidermal growth factor receptors, HER1, HER2 and HER4. Currently, Puma is primarily focused on the commercialization of NERLYNX and the continued development of its other advanced drug candidates directed at the treatment of HER2-positive breast cancer. Puma believes that NERLYNX has clinical application in the potential treatment of several other cancers that over-express or have a mutation in HER2. Further information about Puma Biotechnology can be found at www.pumabiotechnology.com

About Daiichi Sankyo Cancer Enterprise

The vision of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking in order to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by our Antibody Drug Conjugate (ADC) and Acute Myeloid Leukemia (AML) Franchises, our cancer pipeline includes more than 20 small molecules, monoclonal antibodies and ADCs stemming from our powerful research engines: our two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in development include: quizartinib, an oral FLT3 inhibitor, for newly-diagnosed and relapsed or refractory AML with FLT3-ITD mutations; DS-8201, an ADC for HER2-expressing breast and gastric cancer, and other HER2-expressing solid tumors; and pexidartinib, an oral CSF-1R inhibitor, for tenosynovial giant cell tumor (TGCT), which is also being explored in a range of solid tumors in combination with the anti-PD1 immunotherapy pembrolizumab. For more information, please visit: www.DSCancerEnterprise.com.