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Array Announces Agreement To Acquire ENCORAFENIB (LGX818)

On January 23, 2015 Array BioPharma reported that it has reached a definitive agreement with Novartis Pharma AG to acquire worldwide rights to encorafenib (LGX818), a BRAF inhibitor currently in Phase 3 development (Press release Array BioPharma, JAN 23, 2015, View Source [SID:1234501374]). This agreement is conditional on the closing of transactions announced by Novartis and GlaxoSmithKline PLC (GSK) on April 22, 2014, which are expected to close in the first half of 2015, and the agreement remains subject to the receipt of regulatory approvals. Array previously announced a definitive agreement with Novartis to regain global rights to the Phase 3 MEK inhibitor binimetinib, the material terms of which remain in place following this agreement. In order to address competition concerns raised by the European Commission, Array has agreed to obtain an experienced partner for global development and European commercialization of both binimetinib and encorafenib. The European Commission is expected to issue a decision regarding the Novartis-GSK transaction on January 28, 2015.

“Acquiring worldwide rights to encorafenib, an innovative late-stage oncology product, represents a tremendous opportunity for Array,” said Ron Squarer, Chief Executive Officer, Array BioPharma. “There are currently eleven active encorafenib clinical trials, including the Phase 3 COLUMBUS trial in which encorafenib is being studied in combination with binimetinib for BRAF+ melanoma patients. With rights to both encorafenib and binimetinib, Array would enhance its position to broadly develop and commercialize each product, as well as this MEK/BRAF combination, which may have differentiating advantages when compared to available therapies.”

Terms of the Agreement

Upon satisfaction of all conditions and closing of the deal, Array will acquire global rights to encorafenib. Other than a de minimis payment due to Novartis from Array, there are no milestone payments or royalties payable under this agreement by either party. Novartis has agreed to provide transitional regulatory, clinical development and manufacturing services as specified below and will assign or license to Array all patent and other intellectual property rights Novartis owns to the extent relating to encorafenib. As part of the transaction, Array has agreed to obtain an experienced partner for global development and European commercialization of both binimetinib and encorafenib. If Array is unable to find a suitable partner in the prescribed time period, a trustee would have the right to sell such European rights.

Novartis will conduct and fund the COLUMBUS trial through the earlier of June 30, 2016 or completion of last patient first visit. At that time, Array will assume responsibility for the trial, while Novartis will reimburse Array for out-of-pocket costs along with 50% of Array’s full time equivalent (FTE) costs in connection with completing the COLUMBUS trial. Novartis is responsible for conducting all other encorafenib trials until their completion or transfer to Array for a defined transition period. For all trials transferred to Array, Novartis will reimburse Array for out-of-pocket costs and 50% of Array’s FTE costs in connection with completing the trials.

Novartis will supply encorafenib for clinical and commercial use for up to 30 months after closing and will also assist Array in the technology and manufacturing transfer of encorafenib. Novartis will also provide Array continued access to several Novartis pipeline compounds for use in currently ongoing combination studies, and possible future studies, including Phase 3 trials, with encorafenib. The effectiveness of the agreement is subject to the receipt of regulatory approvals and to the consummation of the Novartis-GSK transaction.

In addition, Array agreed to undertake to obtain certain third party consents or waivers necessary for Array to consummate the transactions under the Novartis Agreement.

Advaxis Announces FDA Acceptance of Its Investigational New Drug Application to Commence First-in-Human Clinical Trials of ADXS-HER2

On January 22, 2015 Advaxis reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application to conduct a Phase 1 clinical study of ADXS-HER2 (ADXS31-164) for the treatment of patients with metastatic HER2 expressing solid tumors (Press release Advaxis, JAN 22, 2015, View Source [SID:1234501367]). The clinical trial, which will be the first-in-human study of Advaxis’s lead Lm-LLO immunotherapy product for HER2 expressing cancers, is expected to begin patient enrollment in the first half of 2015. In May 2014, Advaxis was granted orphan drug designation by the FDA for ADXS-HER2 in osteosarcoma.

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The Phase 1 clinical study is designed to evaluate the safety and tolerability of ADXS-HER2 as a monotherapy in patients with metastatic HER2 expressing solid tumors such as breast, gastric, esophageal, and osteosarcoma. Results from the study will be used to determine the future clinical development program of ADXS-HER2.

"We are very pleased to have received FDA acceptance for our ADXS-HER2 IND application and look forward to commencing the Phase 1 clinical study in HER2 expressing solid tumors," stated Daniel J. O’Connor, President and Chief Executive Officer of Advaxis. "This trial will provide important insights about the potential of ADXS-HER2 in HER2 expressing cancers such as breast, gastric, esophageal and osteosarcoma."

The safety and efficacy of ADXS-HER2 is currently being evaluated in an ongoing Phase 1/2 veterinary clinical study in pet dogs with osteosarcoma, conducted by Nicola Mason, BVet.Med, Ph.D., DACVIM, of the University of Pennsylvania School of Veterinary Medicine. To date, dogs treated (n=15) with ADXS-HER2 immunotherapy, after receiving standard of care (amputation and follow up chemotherapy), had a statistically significant overall survival benefit (p=0.032) compared to dogs (n=13) that only received standard of care. Additionally, the preliminary data suggests immune responses induced by ADXS-HER2 targeted pulmonary micrometastases and prevent the development of metastatic disease in the dog’s lungs.

Advaxis has granted exclusive worldwide rights to Aratana Therapeutics (Nasdaq:PETX) to develop and commercialize ADXS-HER2 for the treatment of osteosarcoma in dogs. In July 2014, Aratana filed a U.S. Department of Agriculture (USDA) product license application for ADXS-HER2 for the treatment of canine osteosarcoma and other cancers. While the USDA has no specific obligation to respond within a prescribed timeframe, the companies expect a response within 12 to 18 months from the date the application was filed.

Syncona LLP and UCL Business PLC Announce the Formation of Autolus Limited, a Cancer Immunotherapy Company

On January 22, 2015 Syncona and UCL Business, the wholly-owned technology transfer company of University College London (“UCL”), reported the creation of Autolus Limited (“Autolus”), a biopharmaceutical company focused on the development and commercialisation of next-generation engineered T-cell therapies for haematological and solid tumours (Press release Autolus, JAN 22, 2015, View Source [SID:1234501365]). Autolus is founded upon the work of Dr Martin Pule, an academic clinical haematologist and thought-leader in T-cell engineering. Syncona has committed £30m to Autolus in a Series A financing. Dr Christian Itin, former CEO of Micromet and a leader in the cancer immunotherapy field, has joined the company as Chairman.

Recent clinical trials of engineered T-cell treatments for haematological malignancies performed by various groups suggest that chimeric antigen receptor (“CAR”) T-cells have the potential to transform cancer therapy. Realisation of that potential will require innovative technologies to program the properties of T-cells to increase efficacy and safety, and to access tumour types which are not addressable with the current generation of CAR T-cell technology. Autolus is a next-generation engineered T-cell company, developing a series of CAR T-cell products based on its proprietary targets, constructs and technologies.

Martin Pule, Chief Scientific Officer of Autolus and Senior Lecturer at the UCL Cancer Institute and NIHR University College London Hospitals Biomedical Research Centre, commented:
“It is exciting to be involved in Autolus, where we have an opportunity to bring innovative new therapeutic approaches to patients who often have no alternative treatment path. The key will be to remain at the cutting-edge of T-cell engineering to create a new generation of programmed T-cells acting as autonomous agents to kill tumour cells. What we’ve seen so far in the CAR T-cell field is only the beginning.”

Christian Itin, Chairman of Autolus, said:
“A key element of Autolus’ strategy is to progress CAR T-cell products quickly into clinical trials, leveraging our strong partnership with UCL. The company has engaged a team of thought-leading academics in London as advisors, and will perform its Phase 1 clinical studies and manufacturing within the academic infrastructure of the city, including the integrated cancer clinical trials infrastructure at University College Hospital and the expert cell therapy manufacturing facility at the UCL Institute of Child Health and Great Ormond Street Hospital.”

Edward Hodgkin, Partner with Syncona LLP and Chief Executive Officer of Autolus, added:
“Autolus is a great fit with Syncona’s strategy. We are focussed on building companies in areas of cutting-edge science with the potential to deliver extreme efficacy to patients. CAR T-cell products have the potential to transform cancer therapy, and we expect Autolus to be at the forefront of a revolution in medicine in which human cells are used to treat disease. We have a very talented team and are delighted to have attracted Christian Itin to act as Chairman of the Company.”

Cengiz Tarhan, Managing Director of UCLB, said:
“UCL is a world leader in the biomedical sciences, with an unremitting commitment to outstanding research and translation into healthcare benefits for patients. It is exciting to support these breakthrough treatments being taken forward in a commercial environment in a way that may benefit patients globally. The formation of Autolus represents the culmination of several years of research in the laboratories of Martin Pule and his collaborators drawing on funding from multiple government and charitable sources. UCLB are delighted to be able to partner with Syncona to launch Autolus.”

Curis and Aurigene Announce Collaboration, License and Option Agreement to Discover, Develop and Commercialize Small Molecule Antagonists for Immuno-Oncology and Precision Oncology Targets

On January 21, 2015 Curis and Aurigene reported that they have entered into an exclusive collaboration agreement focused on immuno-oncology and selected precision oncology targets (Press release Curis, JAN 21, 2015, View Source [SID:1234501360]). The collaboration provides for inclusion of multiple programs, with Curis having the option to exclusively license compounds once a development candidate is nominated within each respective program. The partnership draws from each company’s respective areas of expertise, with Aurigene having the responsibility for conducting all discovery and preclinical activities, including IND-enabling studies and providing Phase 1 clinical trial supply, and Curis having responsibility for all clinical development, regulatory and commercialization efforts worldwide, excluding India and Russia, for each program for which it exercises an option to obtain a license.

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The first two programs under the collaboration are an orally-available small molecule antagonist of programmed death ligand-1 (PD-L1) in the immuno-oncology field and an orally-available small molecule inhibitor of Interleukin-1 receptor-associated kinase 4 (IRAK4) in the precision oncology field. Curis expects to exercise its option to obtain exclusive licenses to both programs and file IND applications for a development candidate from each in 2015.

"We are thrilled to partner with Aurigene in seeking to discover, develop and commercialize small molecule drug candidates generated from Aurigene’s novel technology and we believe that this collaboration represents a true transformation for Curis that positions the company for continued growth in the development and eventual commercialization of cancer drugs," said Ali Fattaey, Ph.D., President and Chief Executive Officer of Curis. "The multi-year nature of our collaboration means that the parties have the potential to generate a steady pipeline of novel drug candidates in the coming years. Addressing immune checkpoint pathways is now a well validated strategy to treat human cancers and the ability to target PD-1/PD-L1 and other immune checkpoints with orally available small molecule drugs has the potential to be a distinct and major advancement for patients. Recent studies have also shown that alterations of the MYD88 gene lead to dysregulation of its downstream target IRAK4 in a number of hematologic malignancies, including Waldenström’s Macroglobulinemia and a subset of diffuse large B-cell lymphomas, making IRAK4 an attractive target for the treatment of these cancers. We look forward to advancing these programs into clinical development later this year."

Dr. Fattaey continued, "Aurigene has a long and well-established track record of generating targeted small molecule drug candidates with bio-pharmaceutical collaborators and we have significantly expanded our drug development capabilities as we advance our proprietary drug candidates in currently ongoing clinical studies. We believe that we are well-positioned to advance compounds from this collaboration into clinical development."

CSN Murthy, Chief Executive Officer of Aurigene, said, "We are excited to enter into this exclusive collaboration with Curis under which we intend to discover and develop a number of drug candidates from our chemistry innovations in the most exciting fields of cancer therapy. This unique collaboration is an opportunity for Aurigene to participate in advancing our discoveries into clinical development and beyond, and mutually align interests as provided for in our agreement. Our scientists at Aurigene have established a novel strategy to address immune checkpoint targets using small molecule chemical approaches, and have discovered a number of candidates that modulate these checkpoint pathways, including PD-1/PD-L1. We have established a large panel of preclinical tumor models in immunocompetent mice and can show significant in vivo anti-tumor activity using our small molecule PD-L1 antagonists. We are also in the late stages of selecting a candidate that is a potent and selective inhibitor of the IRAK4 kinase, demonstrating excellent in vivo activity in preclinical tumor models."

In connection with the transaction, Curis has issued to Aurigene approximately 17.1 million shares of its common stock, or 19.9% of its outstanding common stock immediately prior to the transaction, in partial consideration for the rights granted to Curis under the collaboration agreement. The shares issued to Aurigene are subject to a lock-up agreement until January 18, 2017, with a portion of the shares being released from the lock-up in four equal bi-annual installments between now and that date.

The agreement provides that the parties will collaborate exclusively in immuno-oncology for an initial period of approximately two years, with the option for Curis to extend the broad immuno-oncology exclusivity.

In addition Curis has agreed to make payments to Aurigene as follows:

for the first two programs: up to $52.5 million per program, including $42.5 million per program for approval and commercial milestones, plus specified approval milestone payments for additional indications, if any;
for the third and fourth programs: up to $50 million per program, including $42.5 million per program for approval and commercial milestones, plus specified approval milestone payments for additional indications, if any; and
for any program thereafter: up to $140.5 million per program, including $87.5 million per program in approval and commercial milestones, plus specified approval milestone payments for additional indications, if any.

Curis has agreed to pay Aurigene royalties on any net sales ranging from high single digits to 10% in territories where it successfully commercializes products and will also share in amounts that it receives from sublicensees depending upon the stage of development of the respective molecule.

For more information, please refer to the Current Report on Form 8-K filed by Curis with the U.S. Securities & Exchange Commission on January 21, 2015.

Zymeworks Announces Bi-Specific Antibody Collaboration with Celgene

On January 21, 2015 Zymeworks reported a collaboration and licensing agreement with Celgene for the research, development, and commercialization of bi-specific antibody therapeutics enabled using Zymeworks’ proprietary Azymetric platform (Press release Zymeworks, JAN 21, 2015, View Source [SID:1234501366]).

Under the terms of the agreement, Zymeworks and Celgene will collaborate on the research and development of multiple bi-specific antibodies based on the Azymetric platform. Celgene will have the option to advance the resulting bi-specific candidates through clinical development and subsequent commercialization. Zymeworks will receive an initial upfront payment, as well as an equity investment from Celgene. Zymeworks is eligible to receive clinical, regulatory, and commercial milestones on successful candidates totaling up to US $164M per therapeutic candidate. Additionally, Zymeworks will receive royalties on worldwide net sales. Further financial details are not disclosed.

“We are extremely excited to collaborate with Celgene on the development of bi-specific antibodies using the Azymetric platform and believe that this class of biotherapeutics has the potential to create game-changing treatment options for patients with unmet medical needs,” said Ali Tehrani, Ph.D., President & CEO of Zymeworks. “We believe that the upfront revenue from this collaboration, in combination with Celgene’s meaningful equity investment and the proceeds from our recent financing rounds, will help accelerate Zymeworks’ internal oncology pipeline candidates towards multiple INDs in 2016 and beyond.”