On January 11, 2016 Advanced Accelerator Applications S.A. (NASDAQ:AAAP) ("AAA" or "the Company"), an international specialist in molecular nuclear medicine, reported an exclusive license agreement with Johns Hopkins University in Baltimore, Maryland to develop and market PSMA-SR6, a receptor ligand of Prostate-Specific Membrane Antigen (PSMA) for clinical therapeutic and diagnostic purposes (Press release, Johns Hopkins University, JAN 11, 2016, View Source [SID1234524452]). AAA will focus on developing this treatment and its companion diagnostic for prostate cancer through novel molecular nuclear medicine techniques similar to those implemented for the development of Lutathera and Somakit. Prostate cancer affects nearly 1 in 7 men during their lifetime worldwide.

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The terms of the agreement include payment to Johns Hopkins of an upfront licensing fee, as well as certain milestone and royalty payments.

"This licensing agreement is the first step toward broadening our development pipeline by leveraging a formula that we have already successfully applied to develop our lead therapeutic and diagnostic candidates Lutathera and Somakit. We plan to radiolabel PSMA-SR6, to develop a 177Lu-PSMA-SR6 to treat and monitor prostate cancer and a 68Ga-PSMA-SR6, which will help to diagnose and stage disease. The PSMA expression pathway has been widely investigated with labelled antibodies, but we believe that a small molecule, with very high specificity and rapid uptake into tumors and clearance from non-targeted organs could be the ideal candidate for a full theragnostic approach. We are very pleased to partner with the Johns Hopkins University as they have been pioneering and leading this new field for many years," says Stefano Buono, Chief Executive Officer of AAA.

"Our license agreement with AAA extends Johns Hopkins University’s research leadership in PSMA to benefit patients," says Neil Veloso, Executive Director of Johns Hopkins Technology Ventures. "We are very pleased that AAA has selected PSMA-SR6 for full development for commercial applications in an area of significant patient need."

AAA is planning to support a proof-of-concept study in humans that may start in 2016 for both diagnostic and therapeutic applications of PSMA-SR6.

PSMA-SR6 is a unique second-generation selective prostate cancer PSMA receptor ligand developed by Dr Martin Pomper at Johns Hopkins University. PSMA-SR6 has a unique structure and is selective for PSMA expressed on prostate cancer tumor cells. It belongs to a new class of PSMA receptor ligands with high potential as diagnostic and therapeutic markers for prostate cancer. Studies have consistently demonstrated PSMA expression in all types of prostate tissue and an increased PSMA expression in cancer tissue.

On January 11, 2016 Tensha Therapeutics, a privately-held company based in Cambridge, MA, reported it will be acquired by Roche (Press release, Tensha Therapeutics, JAN 11, 2016, View Source [SID1234518479]). Founded by James E. Bradner, MD, of the Dana-Farber Cancer Institute, and managed and funded by HealthCare Ventures, Tensha has developed a pioneering epigenetic technology that disrupts bromodomain and extra terminal domain (BET) proteins in order to develop potential treatments for cancer. The lead product, TEN-010, is a small molecule BET inhibitor that is currently in two Phase 1b clinical trials for the treatment of patients with cancer.

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"BET inhibitors function as targeted therapy in rare cancers with BET gene rearrangements (NUT midline carcinoma), and in common cancers as a means of inhibiting the function of the master growth control genes, such as MYC."
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Under the terms of the agreement, Tensha’s shareholders will receive an upfront cash payment of $115 million, plus additional contingent payments of up to $420 million based on the achievement of certain predetermined clinical and regulatory milestones. The transaction is subject to customary closing conditions and anticipated to close in the first quarter of 2016.

"BET proteins are a highly promising class of therapeutic targets in cancer," said James Bradner, MD, Founder of Tensha, Associate Professor at Harvard Medical School, and Investigator at the Dana-Farber Cancer Institute. "BET inhibitors function as targeted therapy in rare cancers with BET gene rearrangements (NUT midline carcinoma), and in common cancers as a means of inhibiting the function of the master growth control genes, such as MYC."

"We selected TEN-010 as a highly selective, potent BET inhibitor, and we moved rapidly and strategically to advance its development," said Steven Landau, MD, Chief Medical Officer of Tensha and Director of Clinical and Scientific Analysis for HealthCare Ventures. "Our initial clinical data demonstrating the potential of TEN-010 in patients with NUT midline carcinoma was presented at the AACR (Free AACR Whitepaper)/NCI/EORTC conference in November."

"We are very excited about this acquisition, as it moves TEN-010 into the pipeline of a world leader in the development of novel cancer therapeutics. With leadership in solid and hematological tumors and deep understanding of BET biology, Roche is the ideal company to explore the broad clinical potential of TEN-010," said Douglas E. Onsi, Chief Executive Officer of Tensha and Managing Director of HealthCare Ventures. "We appreciate the work of the Bradner lab, the Tensha and HealthCare Ventures employees, and the clinical teams at our trial sites for their important roles in bringing TEN-010 to studies in patients."

About BET Proteins

Bromodomain and extra terminal domain (BET) proteins are central mediators of gene control and cellular memory. In cancer, BET proteins activate growth and survival genes. Further, they contribute to cancer cell memory by binding to the genome as molecular bookmarks. Tensha’s Founder, James Bradner, MD, Associate Professor at the Dana-Farber Cancer Institute and Harvard Medical School, was the first to recognize the broad potential of BET inhibitors as anti-cancer agents. The Bradner lab first reported BET inhibitors in 2010 in Nature magazine, and established the potential of BET inhibitors in solid tumors and blood cancers. With chemist Jun Qi, Bradner thereafter invented TEN-010, a best-in-class BET inhibitor, for clinical development. BET inhibitors function as targeted therapy in rare cancers with BET gene rearrangements (NUT midline carcinoma), and in common cancers as a means of inhibiting the function of the master growth control genes, such as MYC. BET inhibition represents a new paradigm of targeting cellular memory, or epigenetics, in cancer, inflammation, and fibrosis.

On January 11, 2016 AstraZeneca, along with its global biologics research and development arm, MedImmune, and Moderna Therapeutics reported a new collaboration to discover, co-develop and co-commercialize messenger RNA (mRNA) therapeutic candidates for the treatment of a range of cancers (Press release, Moderna Therapeutics, JAN 11, 2016, View Source [SID1234517365]). The collaboration is in addition to the agreement announced by the companies in 2013 to develop mRNA Therapeutics for the treatment of cardiovascular, metabolic and renal diseases as well as selected targets in oncology.

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The collaboration will combine MedImmune’s protein engineering and cancer biology expertise with Moderna’s mRNA platform. mRNA-based therapies are an innovative treatment approach that enables the body to produce therapeutic protein in vivo, opening up new treatment options for a wide range of diseases that cannot be addressed today using existing technologies.

Under the terms of the new agreement, AstraZeneca and Moderna, a pioneer of mRNA Therapeutics, have agreed to collaborate on two specific immuno-oncology programs, based on promising pre-clinical data, including pharmacology in tumor models. Moderna will fund and be responsible for discovery and preclinical development of product candidates, with the aim of delivering one Investigational New Drug (IND) application-ready molecule for each of the two programs. Moderna’s efforts will be led by its oncology-focused venture, Onkaido. AstraZeneca will be responsible for early clinical development, led by MedImmune, and Moderna and AstraZeneca will share the costs of late-stage clinical development. The two companies will co-commercialize resulting products in the US under a 50:50 profit sharing arrangement. AstraZeneca will lead ex-US commercialization efforts, with Moderna receiving tiered royalties up to substantial double digits on ex-US sales.

Pascal Soriot, Chief Executive Officer, AstraZeneca, said: "We’re pleased to be expanding our relationship with Moderna with this new collaboration, to advance the potential of pioneering messenger RNA technology in developing game-changing new treatments for cancer patients."

"Since our companies’ original strategic agreement in March 2013, Moderna’s relationship with AstraZeneca has been very fruitful. This new agreement with AstraZeneca demonstrates the effectiveness of our existing relationship and the power of our mRNA technology," said Stéphane Bancel, Chief Executive Officer of Moderna. "We’re gratified to deepen our relationship with AstraZeneca and MedImmune with this major initiative, and we look forward to getting underway immediately with our new joint immuno-oncology programs."

Under the companies’ original strategic agreement, AstraZeneca holds exclusive access to select any target of its choice in cardiometabolic diseases, as well as select targets in oncology, over a period of up to five years for subsequent development in mRNA. Several projects are progressing towards clinical development under the arrangement, and a first-in-human study is expected to commence in late 2016.

With its novel technology to enable mRNA as a drug, Moderna is building a fully scaled drug discovery and development platform centered on the rapid and low-cost design, delivery and production of mRNA drug candidates. Moderna is also advancing an innovative business model built on the decentralization of drug development activities. With an ecosystem of in-house concept development, ventures focused on therapeutic areas and a cluster of major pharma and biotech partners, Moderna is enabling more than 90 discovery and preclinical programs today across oncology, infectious diseases, rare diseases and cardiovascular diseases. Moderna’s pipeline also covers a broad expanse of novel drug modalities, each representing a distinct approach to using the company’s novel mRNA expression platform to encode proteins that achieve a therapeutic benefit.

On January 11, 2016 Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) reported that the Company expects to significantly improve upon its financial guidance for 2015 (Press release, Isis Pharmaceuticals, JAN 11, 2016, View Source;p=RssLanding&cat=news&id=2128373 [SID:1234508772]). The Company expects to end 2015 with a pro forma net operating loss (NOL) in the low $20 million range and more than $775 million in cash.

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"Over the past several years, we have created a strong and consistent financial foundation. Our corporate partnerships have produced increasing levels of revenue as our partnered programs have matured and expanded. We have been able to support the advancement of our very large pipeline with modest expense growth due to the efficiency of our technology platform as well as the significant in-kind contributions of our partners. With three potentially transformational medicines close to commercialization, we look forward to adding product revenues and royalties to our revenue base over the next few years," said Elizabeth L. Hougen, chief financial officer of Ionis Pharmaceuticals. "We expect to end 2015 with a pro forma NOL in the low $20 million range, which represents a 60% improvement over our original guidance. In addition, we expect to end 2015 with more than $775 million in cash, substantially exceeding our 2014 year-end cash balance and our 2015 cash guidance. Importantly, our significant increase in revenue over the last several years reflects the successes in all of our collaborations as the drugs in those collaborations advanced."

The Company intends to provide financial guidance for 2016 in connection with its year-end 2015 financial results in February.

Pipeline Update
Ionis management will present an update today on its drug development pipeline at the J.P. Morgan conference, including an update on its ongoing open-label Phase 2 clinical study of nusinersen in infants with Type I spinal muscular atrophy (SMA). Previously the company reported data from this study on event-free survival, measures of muscle function and assessments of developmental milestones. The data reported today show continued increases in median event-free survival and muscle function scores. The safety and tolerability profile of nusinersen to date continues to support further development.

In 2015, Ionis added nine new drugs to its pipeline. Already in 2016, the company has added two new drugs to its pipeline: IONIS-BIIB5Rx and IONIS-BIIB6Rx. Both new drugs are being developed together with Biogen and are designed to address undisclosed targets for the treatment of patients with neurodegenerative diseases. Ionis currently has a total of 38 drugs in its pipeline.

"We believe we are just beginning to realize the value we have created. We have three potentially groundbreaking medicines for which we have completed target enrollment in the respective pivotal Phase 3 trials and preparations are underway for each of these drugs for the necessary regulatory filings for marketing authorization. In addition, we and our partners are well along in preparing to commercialize these medicines. As our pipeline continues to mature, we have many other medicines coming along behind these three late-stage drugs," said B. Lynne Parshall, chief operating officer at Ionis. "We have also demonstrated in 2015 that the advances we are making in our technology continue to make better and better medicines, which allows us to expand the application of our drugs to new tissues, new targets and new diseases. All of this sets us up for an exciting and event-filled 2016."

In January 2016, Ionis terminated its license agreement with Sanofi Genzyme for KYNAMRO (mipomersen sodium).

"We are disappointed that we have had to terminate our contract with Genzyme to commercialize KYNAMRO," said Ms. Parshall. "We know that KYNAMRO is an important drug for patients with homozygous FH. Genzyme is continuing to support patients and physicians as we explore other potential commercialization options."

In addition, Ionis announced that results from the Phase 1/2 study with IONIS-AR-2.5Rx in heavily pretreated, late-stage prostate cancer patients demonstrated encouraging data, including several durable reductions in PSA levels. The drug also exhibited a good safety and tolerability profile supportive of continued development. Data from this study will be presented later in the year. Ionis plans to continue the development of IONIS-AR-2.5Rx independent of AstraZeneca.

On January 8, 2016 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported its 2016 business outlook (Filing, 8-K, Advaxis, JAN 11, 2016, View Source [SID:1234508767]). The outlook is intended to provide Advaxis investors with an overview of anticipated events and key milestones for the coming year.

Advaxis made significant strides in its clinical development programs in 2015. Positive data was presented at the 2015 American Gynecological & Obstetrical Society Annual Meeting from a Phase 2 study of lead compound axalimogene filolisbac in metastatic cervical cancer patients (GOG 0265). Axalimogene filolisbac exceeded historical survival rates in a refractory and heterogeneous patient population and, on the basis of this data, allowed the study to move forward into stage two. Advaxis commenced dosing of a Phase 1/2 trial of axalimogene filolisbac in combination with MedImmune’s durvalumab (anti-PD-L1 immune checkpoint inhibitor) for metastatic cervical cancer and head and neck cancer. The Company also began dosing of a Phase 1/2 trial of ADXS-PSA in combination with Merck’s Keytruda (pembrolizumab; anti-PD-1 immune checkpoint inhibitor) for metastatic prostate cancer. A third product candidate, ADXS-HER2, targeting HER2 positive cancers, moved into the clinic and commenced dosing.

Advaxis made significant progress in its business operations, including raising more than $100M in capital. Presented with the challenge of a clinical hold on all of its programs, Advaxis worked closely with the U.S. Food and Drug Administration (FDA) to have the hold lifted in a timely manner.

2016 OPERATIONAL MILESTONES

Advaxis anticipates the following operational milestones in 2016:

Clinical Operations

Axalimogene Filolisbac

● Finish the Special Protocol Assessment (SPA) process and initiate enrollment in a Phase 3 trial for the treatment of high-risk, locally advanced cervical cancer (AIM2CERV) in mid-2016.

● Complete enrollment of stage 2 of GOG 0265 study in patients with metastatic cervical cancer in 2016.

● Initiate Phase 2 study in combination with Incyte’s epacadostat (IDO-1 inhibitor) for the treatment of early stage cervical cancer in the first half of 2016.

● Commence enrollment of Phase 2 trial in metastatic anal cancer (FAWCETT) in the first half of 2016.

● Complete enrollment in the combination Phase 1/2 study with MedImmune’s durvalumab (anti-PD-L1 immune checkpoint inhibitor) for the treatment of HPV-associated head and neck and cervical cancer in late 2016.

● Following the successful completion of cohort 1 of the combination, which occurred in 2015, fully enroll cohort 2 (with a higher dose of durvalumab).

● Following completion of cohort 2, a dose determination will be made and enrollment in the expansion phase of the study will commence in the first half of 2016, with completion of enrollment by the end of 2016.

● Commence and complete enrollment of the Phase 2 dose-escalation study in recurrent cervical cancer (at 1×1010 cfu) in the first half of 2016.

● Present data from a Phase 1/2 window of opportunity trial in HPV-positive head and neck cancer in the first half of 2016 at a major medical meeting.

● Commence enrollment of Phase 2 study in patients with HPV-positive, non-squamous, non-small cell lung cancer following first-line induction chemotherapy via partner in the first half of 2016.

● Commence investigator initiated studies, including for other HPV-associated cancers (e.g., penile and vaginal cancers).

ADXS-PSA

● Complete enrollment of Phase 1/2 study in combination with Merck’s Keytruda (pembrolizumab), an anti-PD-1 immune checkpoint inhibitor, for the treatment of advanced, metastatic castrate-resistant prostate cancer.

● Following the successful completion of dose escalation cohorts 1 and 2, which occurred in 2015, fully enroll cohort 3 (highest dose at 1×1010) in the first half of 2016.

● Once a dose determination is made, enrollment in the Part B combination arm with ADXS-PSA and Keytruda will commence in the first half of 2016, with completion of enrollment by the end of 2016.

ADXS-HER2

● Complete enrollment of Phase 1b dose-escalation study of ADXS-HER2 in patients with HER2-driven malignancies in the first half of 2016.

● Fully enroll Part A, which is designed to establish safe dosing levels in preparation for the expansion phase of the study in HER2-driven malignancies.

● Once a dose is selected from Part A, enrollment in a Part B expansion phase will commence in the second half of 2016.

● Following completion of Part A in the Phase 1b dose escalating study, commence collaboration and cooperative group trial with the Children’s Oncology Group in osteosarcoma.

● Initiate commercialization via Aratana Therapeutics (NASDAQ:PETX) (using the name AT-014) for the treatment of canine osteosarcoma following approval from the U.S. Department of Agriculture (USDA).

Expanding Pipeline

ADXS-NEO

● MINE (My Immunotherapy Neo-Epitopes), a collaboration with Memorial Sloan Kettering Cancer Center, will progress toward the filing of an IND in 2016. MINE uses Advaxis’s Lm Technology to develop neoepitope immunotherapies based on an individual patient’s tumor.

ADXS-TNBC

● Preclinical work will be finalized for ADXS-TNBC, a multiple-antigen construct for Triple Negative Breast Cancer (TNBC) with the goal of filing an IND in 2016.

Enhanced Manufacturing Capabilities

● Advaxis will continue to enhance its internal process/analytical development, quality systems, manufacturing and quality control infrastructure with the goal of accelerating and advancing its pipeline. The company plans to broaden its capabilities through the completion of a new pilot plant, GMP manufacturing facility, research and development labs, and quality control labs. In addition, Advaxis plans to undertake several technology transfers with its partners and install new innovative technologies to reduce lead times and to improve the overall supply chain.

Business Development

● Advaxis will continue to pursue partnerships for its cancer immunotherapy platform to enable additional research in combination with other cancer therapies and novel immunotherapies.

● Advaxis also continues to explore options for retaining a Latin American partner for axalimogene filolisbac to collaborate on co-development and registration in this important region.

SECOND HALF 2015 REVIEW

Since issuing its first half 2015 business update in June, Advaxis achieved several regulatory, clinical, business and operational milestones during the second half of 2015.

Clinical Milestones

Axalimogene Filolisbac

● August 20: Advaxis and MedImmune commenced enrollment in Phase 1/2 trial. First patient was enrolled in a Phase 1/2 study of axalimogene filolisbac in combination with MedImmune’s investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736), for the treatment of patients with advanced, recurrent or refractory HPV-associated cervical cancer and HPV-associated head and neck cancer.

● September 14: U.S. Food and Drug Administration’s (FDA) Office of Orphan Products Development awarded a three-year $1.1 million grant to Baylor College of Medicine for an ongoing Phase 2 trial in HPV-associated oropharynx (throat) cancer.

● September 17: Data from stage 1 of Phase 2 Study (GOG-0265) of ADXS-HPV were presented at 2015 American Gynecological & Obstetrical Society Annual Meeting. In patients with persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRMCC), who have progressed on at least one prior line of systemic therapy, treatment with axalimogene filolisbac resulted in a 38.5 percent 12-month overall survival rate in 26 patients.

● November 9: Poster at the Society for Immunotherapy Cancer annual meeting showed that axalimogene filolisbac may be safely administered with prophylactic antibiotics up to 1 x 1×1010 cfu in patients with PRMCC, a tenfold increase from prior studies.

● December 14: Advaxis receives Orphan Drug Status from the European Medicines Agency for axalimogene filolisbac for the treatment of anal cancer.

ADXS-PSA

● August 5: Movember Foundation and Prostate Cancer Foundation each awarded grants of $1 million to two research projects in metastatic, treatment-resistant prostate cancer.

ADXS-HER2

● September 28: First patient treated in Phase 1b dose-escalation study of Advaxis’s ADXS-HER2 in HER2-expressing solid tumors. The study is the first in-human study of the Lm Technology immunotherapy product for HER2 expressing cancers.

● December 1: Company receives Orphan Drug Status from the European Medicines Agency for axalimogene filolisbac for the treatment of anal cancer.

Business & Operations

Advaxis achieved the following operational milestones in the second half of 2015:

● The company significantly expanded its IP portfolio of new products including ADXS-NEO (neoepitopes) and PSA-2.0. In addition, Advaxis down-scaled its manufacturing process to enable rapid turn-around of ADXS-NEO for clinical use.

● Over the course of 2015, Advaxis expanded its leadership team, deepening its medical, clinical operations, manufacturing and regulatory affairs functions:

● Mayo Pujols, Vice President, Manufacturing

● Thomas W. Hare, Vice President, Clinical Operations

● Bob Ashworth, Vice President, Regulatory Affairs

● June 29: Daniel J. O’Connor received the 2015 Ernst & Young New Jersey Entrepreneur of the Year award.

● July 21: Advaxis received two patents from the United States Patent and Trademark Office (USPTO) of patents with composition of matter claims for ADXS-PSA and methods of use claims for ADXS-HER2.

● August 13: Advaxis appointed Tom Ridge, first Secretary of Homeland Security and 43rd Governor of Pennsylvania, to its board of directors.

● August 26: Advaxis announced a $25M licensing agreement with Knight Therapeutics to help commercialize its three lead drug candidates in Canada.

● September 10: Advaxis was the inaugural recipient of the Medical Visionary Angel Award from the Farrah Fawcett Foundation.

● October 27: Launched Research Collaboration with Memorial Sloan Kettering Cancer Center to develop neo-epitope immunotherapies based on an individual patient’s tumor (MINE).

● November 17: Received $1.6M Tax Credit from New Jersey Technology Business Tax Program.

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