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.

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.

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.

Cancer Research Technology and Cancer Research UK establish team of stem cell experts to beat cancer

On January 14, 2011 Cancer Research UK and its commercial arm Cancer Research Technology (CRT), reported to have established a team of scientists with expertise in cancer stem cell research to identify new targets to detect, monitor and treat cancer (Press release, Cancer Research Technology, JAN 14, 2011, View Source [SID1234523328]).

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The charity has hand-picked four world class research groups to collaborate on an initial two-year research project to unravel the role of cancer stem cells in the development, growth and spread of tumours in breast, prostate and head and neck cancers. The research groups* are led by: Professor Fiona Watt, Cancer Research UK’s Cambridge Research Institute; Dr Robert Clarke, The University of Manchester and Paterson Institute for Cancer Research; Professor Norman Maitland, University of York and Professor Alan Clarke Cardiff University.

It was previously thought that all the cells within a tumour are the same, but it is now known a small number of slow-growing cells do not respond to standard treatments. These ‘cancer stem cells’ are thought to be a cause of resistance to common therapies and the spread of tumour cells to other parts of the body.

Scientists do not yet know how cancer stem cells can be identified and killed. The Cancer Stem Cell Consortium will develop tests and models to refine a common set of known proteins – or biomarkers – present on cancer stem cells across three different tumour types for future drug discovery programmes. The team will also identify new biomarkers as potential targets for the development of new cancer drugs.

Professor Fiona Watt, deputy director of Cancer Research UK’s Cambridge Research Institute and leader of the consortium, said: "Conventional treatments – which do not target cancer stem cells – may shrink a tumour initially but they don’t prevent regrowth or spread of the tumour.

"At the moment there is limited information on the ways scientists could target cancer stem cells. But I hope that knowledge generated by our team of experts will help in the development of potential new therapies to treat difficult to beat cancers."

Initially the project will receive £500,000 from Cancer Research UK for two years. It is hoped each research team will attract an industry partner to bring in additional skills know-how and more funding for longer term research. In return industry partners will benefit through access to the consortium’s latest discoveries and intellectual property and share Cancer Research UK’s expertise in translating scientific discoveries into new cancer treatments.

Once the early development phase is complete, the industrial partner can choose to develop any joint discoveries into compounds with potential to be taken into early clinical trials.

Dr Phil L’Huillier, Cancer Research Technology’s business development director, said: "We’ve selected the world’s leading experts in cancer stem cell research to push the frontiers of knowledge in this important field.

"Targeting cancer stem cells is an important strategy in the fight against cancer. By bringing together industry partners and using our commercial expertise alongside the critical mass of the best brains in science we hope to identify important new leads for the development of new therapies to increase survival from a range of cancers."

Any profits from the success of the projects will be shared between the charity and the research partners involved, with Cancer Research UK re-investing any proceeds in its future research work. The business relationships will be managed by CRT, which has more than 20 years experience in licensing patents and developing opportunities for new cancer drugs and diagnostics, working closely with licensees and the pharmaceutical industry.

This is the second of CRT’s consortia, the first called Senectus Therapeutics Ltd** formed in 2008 to further research into the triggers of cellular senescence – cell aging – a process by which cells irreversibly halt their cell cycle of growth and division.

Harpal Kumar, Cancer Research UK’s chief executive, said: "Cancer stem cells represent an exciting new frontier in our efforts to beat cancer. We urgently need to find new and effective ways to target these cells. This early research will pave the way for our scientists to develop more treatments and help more people survive a diagnosis of cancer – especially people who have aggressive cancers or for whom conventional treatments do not prevent the cancer returning.

"We’re investing in this exciting collaboration made up of world-leading scientists to combine our research expertise with support from industry partners to crack the codes behind the causes and development of cancer."