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Adaptimmune Announces Initiation of Study to Evaluate its New Affinity Enhanced T-Cell Therapy Targeting MAGE-A10 in Patients with NSCLC, the Most Common Form of Lung Cancer

On December 17, 2015 Adaptimmune Therapeutics plc (Nasdaq: ADAP), a leader in the use of TCR engineered T-cell therapy to treat cancer, reported that it has initiated a Phase I/II study of its affinity enhanced T-cell therapy targeting the MAGE-A10 cancer antigen in patients with locally advanced or metastatic (Stage IIIb or IV) non-small cell lung cancer (NSCLC), the most prevalent type of lung cancer representing approximately 85 percent of lung cancers (Press release, Adaptimmune, DEC 17, 2015, http://www.adaptimmune.com/company-news/adaptimmune-announces-initiation-of-study-to-evaluate-its-new-affinity-enhanced-t-cell-therapy-targeting-mage-a10-in-patients-with-nsclc-the-most-common-form-of-lung-cancer/ [SID:1234508591]).

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This will be the first study of Adaptimmune’s unpartnered affinity enhanced T-cell therapy targeting MAGE-A10, a highly immunogenic member of the MAGE-A family of cancer testis antigens. MAGE-A10 is expressed in a number of solid tumor cell types, and the immunogenicity of the MAGE-A10 antigen has been robustly established. Cancer testis antigen expression in cancer is often associated with higher grade tumors.

"The initiation of this study is an important step in our goal to identify and develop new T-cell-based immunotherapeutics to combat non-small cell lung cancer and other cancers, and we are excited to initiate clinical development of another of our promising affinity enhanced TCR therapeutic candidates," said Dr. Rafael Amado, Adaptimmune’s Chief Medical Officer. "We have already seen encouraging clinical responses in certain cancers to our lead T-cell therapeutic candidate, which targets the NY-ESO-1
cancer antigen, demonstrating that it is possible to utilize our proprietary affinity enhancement technology to modify TCRs to so that they target cancer cells effectively. It is our hope that we may one day offer patients suffering from non-small cell lung cancer an efficacious and well-tolerated therapeutic option."

This is an open label, 3+3 dose escalation study of autologous T-cells genetically engineered with an affinity optimized MAGE-A10 TCR in HLAA*0201 and HLA-A*0206 positive patients with stage IIIb or stage IV NSCLC expressing the MAGE-A10 antigen. Though the prevalence of HLA sub-types varies from population to population, the most common in the western world is HLA-A2. Among the HLA-A2 variants, the most prevalent are HLA-A*0201 and HLA-A*0206.

The study is intended to enroll up to 32 patients in leading clinical centers located in the United States and Europe and will assess the safety and tolerability of Adaptimmune’s affinity enhanced T-cell therapy targeting MAGE-A10. Secondary objectives will include the assessment of clinical efficacy, measurements of durability of persistence of MAGE-A10 T-cells in the blood, and exploratory tumor biomarker studies and evaluations of the phenotype and functionality of MAGE-A10 T-cells.

For more information on this clinical trial, visit ClinicalTrials.gov at: View Source (Identifier: NCT02592577).

About NSCLC
Lung cancer is the most common cancer worldwide, and is the leading cause of cancer deaths in both men and women in the United States. Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined. Non-small cell lung cancer or NSCLC is the most common type of lung cancer, representing approximately 85 percent of lung cancers. There are 3 main subtypes of NSCLC. Approximately 40 percent of lung cancers are adenocarcinomas, which start in early versions of the cells that would normally secrete substances such as mucus. This type of lung cancer occurs mainly in current or former smokers, but it is also the most common type of lung cancer seen in non-smokers. Approximately 25 to 30 percent of all lung cancers are squamous cell carcinomas, which start in early versions of squamous cells which line the inside of the airways in the lungs and are generally linked to a history of smoking. Large cell (undifferentiated) carcinoma account for 10 to 15 percent of lung cancers and can appear in any part of the lung.

Fourth clinical trial opened with monalizumab (IPH2201)

On December 17, 2015 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported the opening of the Phase Ib/II trial of monalizumab (previously IPH2201), a first-in-class NKG2A checkpoint inhibitor, in combination with cetuximab in patients with relapsed or metastatic squamous cell cancer of the head and neck (SCCHN) (Press release, Innate Pharma, DEC 17, 2015, View Source [SID:1234508588]). This multicentric trial, which will include up to 70 patients, will be performed in Europe and the United States. It is the second trial testing monalizumab in head and neck cancer, after the monotherapy neo-adjuvant trial opened in 2014.

Pierre Dodion, MD, Chief Medical Officer at Innate Pharma, said: "HLA-E is frequently expressed by head and neck cancer cells. Monalizumab is a new checkpoint inhibitor targeting both T and NK cells and preventing their inhibition by HLA-E on tumor cells. Furthermore, monalizumab enhances antibody dependent cellular cytotoxicity (ADCC), one of the mechanisms of action of cetuximab, setting a sound rationale for their combination". He added: "All trials from Innate’s initial clinical development plan are now recruiting patients, involving reference centers. We look forward to continuing on expanding this plan to fully explore the potential of monalizumab".

Dr. Roger Cohen, Associate Director of Clinical Research at the Abramson Cancer Center and Professor of Medicine at the Hospital of the University of Pennsylvania, and lead investigator for the study, said: "Cetuximab is the only targeted therapy approved in recurrent/metastatic head and neck cancer. However, its response rate of about 13% and response duration of less than 6 months leave a significant unmet medical need for this patient population. Immuno-oncology could play a key role in the treatment of head and neck cancer, as demonstrated by a variety of emerging and very promising data. The combination of monalizumab and cetuximab could enhance the efficacy of cetuximab by activating the immune system. This is a very appealing dual mechanism rationale".

This trial is part of a global co-development and commercialization agreement with AstraZeneca for monalizumab. Within this framework, four Phase I/II trials are ongoing: the cetuximab combination trial in SCCHN, two single agent trials respectively in SCCHN and in ovarian cancer*, and a combination trial with ibrutinib in chronic lymphocytic leukemia. The co-development plan also includes a combination clinical trial with monalizumab and durvalumab (MEDI4736), a PD-L1 immune checkpoint inhibitor, in solid tumors, which will be performed by AstraZeneca/MedImmune.

LIGAND TO ACQUIRE OMT, INC., A LEADER IN HUMAN ANTIBODY GENERATION, FOR $178 MILLION IN CASH AND STOCK

On December 17, 2015 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) and OMT, Inc. (Open Monoclonal Technology) reported the signing of agreements for Ligand to acquire OMT, Inc., a leader in genetic engineering of animals for the generation of human therapeutic antibodies through its OmniAb platform (Press release, Ligand, DEC 17, 2015, View Source [SID1234526561]).

OMT has leading antibody drug discovery technology and is believed to be the only company in the world offering three transgenic animal platforms for license. Its license agreements with biotechnology partners will initially add 16 shots on goal to Ligand, as well as future potential licensing deals and additional compounds generated from existing partnerships. OMT has existing licenses with Amgen, Celgene, Genmab, Janssen, Merck KGaA, Pfizer, Seattle Genetics, Five Prime, Symphogen and various other biotechnology and pharmaceutical companies. OMT is privately held and is majority owned by Essex Woodlands.

Under the terms of the transaction, Ligand will pay OMT shareholders approximately $178 million, including $92.6 million in cash and $85.4 million in Ligand common stock. Roland Buelow, Ph.D., founder of OMT and a world-renowned antibody researcher, is expected to join Ligand as Vice President of Antibody Technologies and continue working with Ligand on advancing the OMT business. The transaction is subject to customary closing conditions and is expected to close in January 2016.

"OMT is an ideal strategic fit for Ligand and holds potential to have a profoundly positive impact on our business over the long term," said John Higgins, Chief Executive Officer of Ligand Pharmaceuticals. "OMT brings a robust and important technology for biologic drug discovery that we believe will stand next to Captisol in terms of opportunity for partner events, new licensing transactions and financial contribution. The transaction is expected to be accretive to revenue and adjusted earnings, and if products are approved in the future, the underlying royalties could generate substantial revenues for decades to come. This transaction is a major addition to what Ligand believes is an unprecedented portfolio of more than 140 fully-funded partnered programs."

"OMT has created a highly successful business around the OmniAb antibody technology platform and the business has significant growth potential," said Roland Buelow, Ph.D., Chief Executive Officer of OMT. "We are very impressed with Ligand’s business model, success in deal making and commitment to continue driving the OMT business to even greater success. We believe Ligand’s broad licensing network, business acumen, financial resources and commitment to our technology create an attractive exit for OMT shareholders. I am personally excited to join Ligand as an employee and shareholder, and look forward to helping the talented team continue to expand its business."

OMT OmniAb Antibody Platform

OmniAb refers to three industry-recognized transgenic animal platforms for generation of naturally optimized monospecific, bispecific and polyspecific human therapeutic antibodies.

OmniRat is one of the industry’s first human monoclonal antibody technology based on rats. It has a complete immune system with a diverse antibody repertoire and is genetically engineered to produce antibodies with human idiotypes.

OmniMouse is a transgenic mouse that complements OmniRat and expands epitope coverage and therefore antibody discovery capabilities for partners.

OmniFlic is an engineered rat with a fixed light chain for development of bispecific, fully human antibodies.

All three platforms use patented technology and deliver fully human antibodies with high affinity, specificity, expression, solubility and stability, thereby facilitating more rapid discovery of therapeutic antibodies for partners. OmniAb allows partners to identify high-affinity antibodies in a patented animal system, that therefore have been optimized by in vivo selection pressures, accelerating development times and increasing the prospects of technical success compared with traditional antibody-generation technologies.

Antibodies are a major and growing segment of the pharmaceutical industry. Five of the top 10 selling medicines in 2014 were antibodies. The top 10 selling antibodies in 2014 generated total revenue of $57 billion and the number of antibodies in clinical development has tripled over the past seven years from 150 to 468 currently.

Acquisition Rationale

There are multiple aspects of this transaction that support the strategic rationale to Ligand, including:

1. Financial Contribution – Projected to be accretive to revenues and adjusted earnings with potential for significant financial contribution to Ligand through future royalties.

2. Portfolio Expansion – Major addition of new partners and fully-funded shots on goal. OMT is expected to initially bring to Ligand 16 new shots on goal, and Ligand is projected to have more than 140 fully-funded programs and more than 83 partners after the OMT transaction closes.

3. Technology Diversification – Diversification of Ligand’s technology offering for licensing. OmniAb is a broad and robust technology platform and is a key resource used by biotechnology companies to discover new biologic drugs. The OMT technology is expected to be a new pillar of Ligand’s business, standing alongside the Captisol drug-formulation technology. OmniAb will create a strong platform for Ligand to seek new licenses and partnerships.

4. Royalty Extension – Significant extension of potential patent protection period and royalty terms for Ligand-partnered programs. Patents for OMT technology run through 2033, but each newly discovered antibody may be the basis for its own novel intellectual property, resulting in patents for each antibody on a drug-by-drug basis that could extend past 2040.

Acquisition and OMT Business Highlights

Following are some of the highlights of the OMT business and their expected impact on Ligand:

OMT diversifies Ligand’s business by adding a proprietary antibody-generating platform, giving Ligand further exposure to an important segment of the pharmaceutical industry. OMT has three distinct transgenic rodent systems for generating antibodies: OmniRat, OmniMouse and OmniFlic.
Ligand projects up to three antibodies from the OMT platform will be in human Phase 1 trials by the end of 2017 and as many as 15 antibodies could be in Phase 1 or more advanced trials by 2020.
OMT OmniAb licenses have generally been structured with a combination of license fees, annual technology access fees, milestone payments and royalties. Royalties are generally in the low- to mid-single digits. The existing OMT portfolio is comprised of platform licenses with high-quality companies.
With the acquisition, Ligand is acquiring 16 platform partnerships and antibody-specific licenses. Following the transaction, Ligand will have partnerships with 83 different companies and over 140 fully funded programs with each OMT platform deal currently counting as one shot on goal.
The OMT business is projected to add $6 million and $12 million of revenues to Ligand in 2016 and 2017, respectively. This revenue is based on existing licensing contracts and potential payments, and does not include revenue from potential new partnerships and programs. Annual expenses to operate the OMT business are projected to be between $3 million and $5 million.
The acquisition of the existing OMT business and licenses will accelerate Ligand’s projected financial growth. The transaction is projected to add 5% to 2016 revenue and 7% to 10% to annual revenue over the next decade, after which time initial royalty-bearing products could be approved with contribution to revenue growth being potentially much greater thereafter. The transaction is projected to be slightly accretive to adjusted EPS in 2016 and accretive to adjusted EPS by approximately 4% to 8% per year over the next several years.
Ligand Pro Forma 2016 and 2017 Financial Outlook

Including this acquisition, Ligand expects 2016 total revenues to be between $113 million and $117 million. This guidance assumes approximately $6 million of revenue from the OMT business in 2016, and approximately $107 million to $111 million of revenue from the original Ligand business. Ligand’s pro forma 2016 cash operating expenses are expected to be between $26 million and $28 million. In 2016, adjusted EPS is projected to be unchanged and in the range of $3.33 to $3.38.

For 2017, Ligand expects total revenues to exceed $158 million with adjusted EPS of more than $4.95. This guidance assumes approximately $12 million of revenue from the OMT business in 2017, and approximately $0.20 of incremental EPS contribution from the acquisition.

OMT non-cash amortization expense estimates are expected to be determined in the near term. Amortization charges will be recognized in GAAP EPS and the non-cash charge will be excluded from adjusted EPS.

Adjusted Financial Measures

The adjusted financial measures discussed above exclude changes in contingent liabilities, mark-to-market adjustment for amounts owed to licensors, non-cash stock-based compensation expense, non-cash debt-related costs, pro-rata non-cash net losses of Viking Therapeutics, non-cash OMT purchase price amortization and non-cash tax expense.

Ligand believes that the presentation of adjusted financial measures provides useful supplementary information to investors and reflects amounts that are more closely aligned with the cash profits for the period as the items that are excluded from adjusted net income are all non-cash items. Ligand uses these adjusted financial measures in connection with its own budgeting and financial planning. These adjusted financial measures are in addition to, and not a substitute for, or superior to, measures of financial performance prepared in conformity with GAAP.

Cellectar Biosciences and Pierre Fabre Laboratories Announce Oncology Research Collaboration

On December 17, 2015 Pierre Fabre, the third largest French pharmaceutical company, and Cellectar Biosciences, Inc. (NASDAQ:CLRB), an oncology-focused biotechnology company, reported a research collaboration designed to combine Cellectar’s proprietary PDC delivery platform with a selection of Pierre Fabre’s proprietary cytotoxics (Press release, Pierre Fabre, DEC 17, 2015, View Source [SID:1234508594]).

These new Small-Molecule-Drug-Conjugate products (SMDCs) are designed to exhibit high selectivity towards cancer cells in order to expand therapeutic index and provide improved clinical performance to otherwise highly potent agents.

Phospholipid Drug Conjugates (PDCs) are a new class of small-molecules that employ Cellectar’s extensively validated phospholipid ether-based cancer targeting and delivery vehicle. The PDC platform possesses the ability to incorporate diverse oncologic payloads for targeted delivery to a broad range of solid and liquid tumours, including brain metastases, and to cancer stem cells.

The primary objective of the research collaboration is to co-design a library of constructs and to achieve in-vivo Proof-of-Concept of the superiority of these PDCs to the corresponding naked payloads. Thanks to their remarkable lipid rafts-mediated distribution properties, PDCs are expected to provide enhanced therapeutic indices to otherwise highly potent payloads through targeted delivery to cancer cells.

Pierre Fabre will provide the payloads and its know-how in the design of natural product-derived active conjugates, as well as its prior expertise into SMDCs. Cellectar will provide its proprietary PDC Platform technology and will be in charge of conducting the drug discovery program up to preclinical stage and, should it be successful, to clinical evaluation. Pierre Fabre has been granted the option to license any, or all, of the new drug conjugates developed as part of the research collaboration, while Cellectar will own all intellectual property (IP) associated with the new drug conjugates.

AstraZeneca enhances long-term growth through Oncology investment in Acerta Pharma

On December 17, 2015 AstraZeneca reported that it has entered into an agreement to invest in a majority equity stake in Acerta Pharma, a privately-owned biopharmaceutical company based in the Netherlands and US (Press release, AstraZeneca, DEC 17, 2015, View Source [SID:1234508592]).

The transaction provides AstraZeneca with a potential best-in-class irreversible oral Bruton’s tyrosine kinase (BTK) inhibitor, acalabrutinib (ACP-196), currently in Phase III development for B-cell blood cancers and in Phase I/II clinical trials in multiple solid tumours.

Pascal Soriot, Chief Executive Officer of AstraZeneca, said: "The investment is consistent with our focus on long-term growth and reflects the role targeted business development plays in our business model. We are boosting a key area in our comprehensive oncology portfolio with a late-stage, potential best-in-class medicine that could transform treatment for patients across a range of blood cancers."

"Acalabrutinib provides us with a small molecule presence in blood cancers to complement our existing immunotherapy approach, in collaboration with Celgene in haematological malignancies. Furthermore, we look forward to working closely with the Acerta team and benefiting from the considerable clinical expertise they bring in this complex area of medicine."

Under the terms of the agreement, AstraZeneca will acquire 55% of the entire issued share capital of Acerta for an upfront payment of $2.5 billion. A further unconditional payment of $1.5 billion will be paid either on receipt of the first regulatory approval for acalabrutinib for any indication in the US, or the end of 2018, depending on which is first. The agreement also includes options which, if exercised, provide the opportunity for Acerta shareholders to sell, and AstraZeneca to buy, the remaining 45% of shares in Acerta. The options can be exercised at various points in time, conditional on the first approval of acalabrutinib in both the US and Europe and when the extent of the commercial opportunity has been fully established, at a price of approximately $3 billion net of certain costs and payments incurred by AstraZeneca and net of agreed future adjusting items, using a pre-agreed pricing mechanism.

An extensive development programme is underway for acalabrutinib with the opportunity for initial regulatory submissions in the second half of 2016 for the treatment of patients with specific types of haematological malignancies. Expanding further into B-cell cancers, acalabrutinib is estimated to reach potential peak-year sales in excess of $5 billion globally. AstraZeneca will also benefit from the substantial expertise in haematological cancers offered by Acerta’s approximately 150 employees.

The BTK inhibitor class is transforming the treatment of B-cell blood cancers, allowing a potentially more effective treatment option with limited side effects, replacing current chemotherapy and antibody-containing regimens. Acalabrutinib is a highly selective, irreversible, next-generation small molecule oral BTK inhibitor supported by strong clinical evidence, with approximately 1,000 patients treated to date, of whom more than 600 were on the potential medicine as monotherapy. Data indicate that acalabrutinib offers enhanced BTK inhibition. Phase I/II data presented at the recent American Society of Haematology Annual Meeting 2015 showed a 95% response rate in patients with relapsed chronic lymphocytic leukaemia, the most prevalent form of adult leukaemia, and a 100% overall response rate in the difficult-to-treat 17p deletion patients1.

In addition, acalabrutinib has the potential to address an unmet medical need for patients who are intolerant to or unsuitable for first generation BTK inhibitor treatment. Currently 20-30% of patients discontinue first-generation therapy due to tolerability issues2.

John C. Byrd MD, Professor and Director, Division of Haematology, Department of Medicine, at The Ohio State University School of Medicine, said: "The BTK inhibitor class has been transformational in the management of B-cell cancers but a portion of patients treated with ibrutinib (the first generation BTK inhibitor), can’t tolerate the side effects and sadly discontinue their treatment. The acalabrutinib data are highly encouraging as they show that high selectivity, a short half-life and an optimised dosing schedule result in very high efficacy and a significantly better tolerability profile with very low discontinuation rates. Acalabrutinib may potentially offer improved long-term benefit over other options available for these patients."

In addition to blood cancers, acalabrutinib is currently being explored in Phase I/II studies in combination with immunotherapy or chemotherapies in a range of solid tumours. Pre-clinical data show that acalabrutinib has an immune-modulatory effect that, as monotherapy and alongside PD-1/PD-L1 antibodies, has the potential to enhance anti-tumour activity.

Acerta will initially be a majority owned subsidiary of AstraZeneca; if AstraZeneca acquires the remaining shares of the company in the future, Acerta would become a wholly-owned subsidiary. The transaction will be accounted for as a business combination and is expected to complete by the end of the first quarter of 2016, subject to customary closing conditions. The initial acquisition payment of $2.5 billion will be funded from cash and debt. The agreement is expected to be moderately dilutive to AstraZeneca’s core earnings in the near term.