Agreement reached to identify a predictive biomarker for PARP inhibitor therapies

On February 2, 2011 MDxHealth SA (NYSE Euronext: MDXH), a leading molecular diagnostics company in the field of personalized cancer treatment, reported that it has signed an agreement with Newcastle University (UK), Cancer Research Technology Limited (CRT) and Pfizer Inc. to collaborate on the identification and development of a biomarker predicting response to Pfizer, CRT and Newcastle University’s drug candidate for PARP inhibition, PF-01367338 (Press release, Cancer Research Technology, FEB 2, 2011, View Source [SID1234523327]). The partners believe identification of a successful predictive biomarker could lead to the development of a companion diagnostic to guide treatment decisions in ovarian and breast cancers.

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"MDxHealth’s methylation platform is potentially suited for the development of companion diagnostics in a wide range of cancer indications," said Jan Groen, chief executive officer of MDxHealth. "Our advanced capabilities run from discovery to proof of principle, using deep sequencing at our new Ghent facility, to assay development and clinical trial testing at our ISO-certified Liege laboratories. We offer a platform that has been tried and tested and is highly attractive for our partners. This and similar agreements with other pharmaceutical companies and academic institutions build on our strong capabilities in the exciting and rapidly emerging field of companion diagnostics."

PF-01367338 works by inhibiting PARP1 and PARP2, enzymes involved in cellular DNA damage repair (DDR). As part of the collaboration, MDxHealth will profile the methylation patterns of DDR genes to identify those involved in predicting tumor development and response to PARP inhibition. MDxHealth’s aim is to ultimately set up a high throughput platform that is clinically validated to rapidly test for epigenetic defects in key DDR genes to support the design and implementation of clinical trials to enable development of optimized, targeted therapies.

Financial terms of the agreement were not disclosed. MDxHealth will provide biomarker discovery services, assay development services, clinical trial testing, and will retain rights to any methylation-based commercial companion diagnostic test that may result from this collaboration. Newcastle University, through research groups led by Professor Nicola Curtin and Dr. Richard Edmondson, will participate in biomarker discovery and validation activities. CRT will have rights to develop and commercialise new biomarkers in other fields. Pfizer will contribute experimental and intellectual input through its translational research team in addition to funding the collaboration.

LIGAND ACQUIRES CYDEX PHARMACEUTICALS

On January 26, 2011 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported it has acquired privately held CyDex Pharmaceuticals, Inc. for a combination of cash and contingent payments (Press release, Ligand, JAN 26, 2011, View Source [SID1234517134]). CyDex, based in Lenexa, Kansas, had 2010 revenue of $16.3 million and EBITDA of $7.6 million, and will operate as a wholly-owned subsidiary of Ligand.

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CyDex shareholders will receive $31.2 million for the merger in upfront cash, a $4.3 million cash payment on the one year anniversary of closing, and will be entitled to contingent cash payments related to certain transactions and pursuant to a revenue share plan. In addition, Ligand paid approximately $800,000 at close for an adjustment for working capital.

"This transformational acquisition accelerates Ligand’s financial growth and provides a unique and broad basket of new assets to further expand our business and long-term potential," said John Higgins, President and Chief Executive Officer of Ligand. "Ligand will now combine the royalties from seven marketed drugs, along with the substantial revenue from the selling of Captisol(R), to advance Ligand toward its goal of turning cash-flow positive with substantial future growth opportunities. This growth will be largely fueled by what Ligand believes is an industry unprecedented portfolio of more than 50 fully-funded partnered development programs, creating a myriad of new revenue stream possibilities."

"CyDex has created a very successful business around the Captisol drug reformulation technology over the last several years and the company has significant growth potential," said Ted Odlaug, former President and Chief Executive Officer of CyDex Pharmaceuticals. "We are very impressed with Ligand’s business model, success in deal making and commitment to continue driving the CyDex business to even greater success. We believe Ligand’s broad licensing network and business acumen, coupled with the opportunity to share in future upside in the business, created an attractive exit for CyDex shareholders."

Acquisition Rationale

The acquisition of CyDex’ cash-flow positive business will accelerate Ligand’s projected financial growth.

— Ligand’s projected 2011 revenue is expected to more than double versus
Ligand’s stand-alone revenue as a result of the transaction, not
including any new licensing revenue (i.e. SARM) or accelerated growth in
Promacta(R) royalties.

Ligand’s asset portfolio (including development stage programs and marketed drugs) will greatly expand to more than 60 programs, significantly increasing the opportunity for new revenue streams over the next few years.

— The existing CyDex portfolio includes numerous high-quality license and
royalty bearing agreements, including Onyx Pharmaceuticals for
carfilzomib and Prism for Nexterone(R).
— Post-merger corporate portfolio is comprised of 7 marketed drugs and
more than 50 fully funded partnered collaborations.

CyDex diversifies Ligand’s business by adding a proprietary and well-validated platform in the increasingly important drug reformulation segment of the pharmaceutical industry.

— Ligand believes that drug reformulation has become an increasingly
valuable solution to the issues related to market erosion due to generic
competition and continued clinical and regulatory uncertainty.

CyDex Brings the Following to Ligand:

Significant Annual Revenue – CyDex currently generates annual revenue from four marketed drugs, material sales from the selling of Captisol, and license and milestone payments.

Onyx Collaboration – CyDex and Onyx Pharmaceuticals entered into a collaboration in 2005 (originally with Proteolix) to develop the Captisol-enabled IV formulation of carfilzomib for refractory multiple myeloma. Onyx has recently reported positive Phase II data for this program and plans to file an NDA in 2011 with the FDA. CyDex is eligible to receive milestones, royalties and Captisol material sales revenue from this program.

Prism Collaboration – Prism Pharmaceuticals recently received marketing approval from the FDA for the Captisol-enabled IV form of amiodarone, to be marketed as Nexterone. Prism plans to launch Nexterone in the near term. Nexterone was developed by CyDex and licensed to Prism in 2007. CyDex is eligible to receive milestones, royalties, and Captisol material sales revenue from this program.

Large Pharma Captisol-Supply Relationships – CyDex currently has multiple material sales collaborations with undisclosed large pharmaceutical companies. These collaborations have Captisol-enabled drugs in clinical development and CyDex anticipates selling Captisol to these partners in the coming years for clinical and commercial use.

Industry Recognized Captisol Technology Brand – Captisol is recognized in the pharmaceutical industry as a powerful answer to the solubility challenges frequently faced by drug-development companies. CyDex’ success is primarily based on solving drug formulation problems, particularly in the area of IV and topical formulations. CyDex has also developed an extensive Drug Master File (DMF) to which its partners can refer when filing with regulatory agencies around the world, adding significant value to the Captisol brand.

Internal Pipeline of Captisol-Enabled Drugs – CyDex is currently developing four proprietary Captisol-enabled drugs for future potential licensing:

— Clopidogrel IV in Phase I for thrombosis
— Melphalan IV in Phase II for stem cell conditioning
— Budesonide/Azelastine nasal in Phase II for seasonal rhinitis
— Topiramate IV in Phase I development for epilepsy

Acquisition Funding

The upfront acquisition payment to CyDex shareholders is comprised of $11.2 million of Ligand’s internal cash and $20 million borrowed on a 42-month secured term loan from Oxford Finance Corporation. Oxford is a specialty lender that has originated loans ranging from $500,000 to $40 million to more than 200 companies. Ligand is also exploring additional financing options for up to a further $10 million in borrowing, for a potential total borrowing of $30 million.

2011 Financial Outlook

For 2011, Ligand expects total revenues to be $22 million to $24 million. The guidance assumes approximately $13 million to $14 million of revenue (partial year accounting) from the CyDex business, and approximately $9 million to $10 million of revenue from the original Ligand business, before any revenue for new licensing agreements.

Ligand’s 2011 operating expenses are expected to be $16 million to $18 million, with an average cost of goods as a percentage of material sales to be approximately 35%. CyDex non-cash amortization expense estimates are expected to be determined in the near-term. If Ligand borrows an additional $10 million during 2011, it anticipates ending 2011 with approximately $20 million of cash. By the end of 2011, Ligand expects its operations to be profitable and cash-flow positive.

MENTRIK Biotech, LLC Acquires Fully Humanized Anti-CD20 Antibody(AME133) from Eli Lilly & CO

On January 26, 2011 MENTRIK Biotech, LLC reported the successful acquisition of AME-133 (LY2469298), an anti-CD20 monoclonal antibody under development for cancer treatment of B-cell non- Hodgkin’s lymphoma and other indications (Press release, Mentrik Biotech, JAN 26, 2011, View Source [SID:1234513567]). AME-133 is an intravenously administered, fully humanized, fc engineered, high-affinity immunoglobulin G subclass (IgG1) monoclonal antibody for which Phase I clinical development has been completed. The CD20 antigen is a validated target for the treatment of patients with B-cell cancers like lymphoma, chronic lymphocytic leukemia (CLL), and for auto-immune diseases like rheumatoid arthritis (RA). Rituximab (Rituxan), a first-generation human-mouse chimeric antibody has been approved by the FDA for the treatment of non- Hodgkin’s lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis. AME-133 is a fully humanized antibody and has been optimized through protein engineering both for increased affinity for CD20 and increased effector function in antibody-dependent cell-mediated cytotoxicity (ADCC), which may lead to superior efficacy and safety.

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A Phase I/II clinical trial with AME-133 for the treatment of patients with previously treated follicular lymphoma has been completed. Sixty-seven patients were treated with AME-133 in this trial. The results showed that AME- 133 is well tolerated and 375mg/m2 was confirmed as the recommended dose for future trials. "We are very excited about this acquisition. The clinical results to date suggest that AME-133 has the potential to improve therapeutic options for patients with follicular lymphomas," says Dr. Vinay Jain, CEO of MENTRIK Biotech.

MENTRIK acquired full rights to develop AME-133 for all human therapeutic, prophylactic, and diagnostic uses. The company intends to continue the development of AME-133 for the treatment of B-cell lymphomas such as non- Hodgkin’s lymphoma, Hodgkin’s disease, Waldenstrom’s macroglobulinemia, Mantle cell lymphoma, and also chronic lymphocytic leukemia (CLL). In addition, MENTRIK will also investigate the potential clinical benefit of AME-133 for the treatment of auto-immune diseases like rheumatoid arthritis and multiple sclerosis.

Theraclone and Pfizer Enter into Infectious Disease and Cancer Antibody Discovery Collaboration

On January 19, 2011 Theraclone Sciences reported that they have entered into a multi-year research and development collaboration with Pfizer (Press release Theraclone Sciences, JAN 19, 2011, View Source [SID:1234500951]). The collaboration will use Theraclone’s I-STAR technology to discover broadly protective monoclonal antibodies against up to four undisclosed targets in the areas of infectious disease and cancer. I-STAR technology is used to screen and identify novel human antibodies to pathogenic agents and endogenous therapeutic targets and is unique in its ability to rapidly test the function of tens of thousands of natural human antibodies and find those with exceptional biologic activity.
Under the terms of the agreement, Theraclone and Pfizer will embark on a discovery program to identify broadly reactive antibodies directed against up to two infectious disease targets and up to two cancer targets. Pfizer will receive an exclusive worldwide license to any therapeutic antibodies discovered under the collaboration. Theraclone is eligible to receive undisclosed royalties on sales of any developed products and up to $632 million in research funding and milestone payments upon the achievement of discovery, development, regulatory and commercialization milestones. Pfizer will be responsible for preclinical and clinical development of the antibodies.

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Philogen IPO pulled as Bayer exits cancer pact

On January 15, 2011 Bayer reported that an eagerly-anticipated initial public offering by the Swiss-Italian biotech Philogen has been cancelled at the last minute after partner Bayer pulled out of their oncology collaboration (Press release, Bayer, JAN 15, 2011, View Source [SID1234564248]).

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Philogen planned to list on the Milan Stock Exchange this Friday (February 18) and was looking to sell a 23% stake. This would have raised between 50.9-65.3 million euros, valuing the group at 170.9-219.5 million euros.

However the Siena-based firm, whose Philochem R&D unit is headquartered in Zurich, has withdrawn the tender offer. This is directly as a result of the "unexpected" decision by Bayer to terminate licence agreements and product development pacts for the cancer treatments radretumab and darleukin, which are in Phase II.

Bayer has not given any details for its withdrawal and told PharmaTimes World News simply that "we have sent a letter to Philogen informing them about our decision to terminate our licence agreement". The latter firm said that such a "material change" to its position had left bookrunners "unwilling to continue with the listing". Philogen also pulled a proposed IPO in 2008 due to market conditions.

Observers were watching with interest to see how the offering would go as it would have been Europe’s first biotechnology IPO in 2011. It would have provided an interesting guide to sentiment among the investment community for a sector that has been struggling to raise funds of late.