DRUG DISCOVERY PROGRAMMES OF CANCER RESEARCH UK AND CANCER RESEARCH TECHNOLOGY SHOWCASED AT AACR-NCI

On November 17, 2008 Cancer Research Technology (CRT) reported that it is hosting thirty-five industrial scientists, representing the research and drug discovery functions of eighteen of the world’s top pharmaceutical and biotechnology companies, during the AACR (Free AACR Whitepaper)-NCI-EORTC Molecular Targets and Cancer Therapeutics meeting in Boston (Press release, Cancer Research Technology, NOV 17, 2009, View Source [SID1234523530]). The objective of the "Science & Seafood" luncheon is to introduce scientific leaders responsible for companies’ cancer drug discovery and development to Cancer Research UK and Cancer Research Technology’s drug discovery programmes. The event features presentations by two of the charity’s leading translational scientists, Professors Paul Workman and Peter Parker.

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Cancer Research UK – the world’s largest independent organisation dedicated to cancer research, invested £303 million last year (2008/09) on research.

LIGAND TO ACQUIRE METABASIS FOR CASH AND CONTINGENT VALUE RIGHTS

On October 27, 2016 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) and Metabasis Therapeutics, Inc. (NASDAQ: MBRX) reported they have entered into a definitive merger agreement under which Ligand will acquire all of the outstanding shares of Metabasis (Press release, Ligand, OCT 27, 2009, View Source [SID:1234510805]).

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Under the transaction, Metabasis stockholders will receive a cash payment at the closing of the transaction of approximately $3.2 million, less Metabasis’ estimated net liabilities at closing and an amount to be deposited in the stockholders’ representative’s fund (Metabasis currently estimates the closing payment to be approximately $1.8 million in cash). In addition, Metabasis stockholders will receive for each Metabasis share four tradable Contingent Value Rights ("CVRs") that will be registered on a Form S-4 registration statement to be filed by Ligand with the Securities and Exchange Commission. The CVRs will entitle Metabasis stockholders to cash payments as frequently as every six months as cash is received by Ligand from proceeds from the sale or partnering of any of the Metabasis drug development programs, among other triggering events. Ligand has committed to spend at least $8 million in new research and development funding on the Metabasis programs within 42 months following the closing of the transaction.

The Ligand and Metabasis Boards of Directors have unanimously voted in favor of the transaction. Stockholders of Metabasis representing approximately 29% of the outstanding shares of Metabasis have signed voting agreements in support of the transaction. Merriman Curhan Ford acted as financial advisor to Metabasis with respect to this transaction.

"This transaction utilizes a creative structure that we believe is potentially highly beneficial to the stockholders of both companies," said John L. Higgins, President and Chief Executive Officer of Ligand Pharmaceuticals. "Ligand obtains numerous high-quality partnered and development-stage programs that will increase our revenue potential and expand our pipeline of proprietary assets. In exchange, the non-partnered Metabasis programs will be advanced by a company with strong and proven research credentials, with the goal of generating cash proceeds payable directly to Metabasis stockholders. If any or all of the Metabasis programs are financially successful, stockholders at both companies will benefit meaningfully from their shared participation in the programs."

Mark D. Erion, Ph.D., President, Chief Executive Officer and Chief Scientific Officer of Metabasis, stated, "Metabasis has built a pipeline of product candidates and drug development programs that have the potential to one day yield new therapies for metabolic and chronic liver diseases, but due to our limited financial and operational resources, we are unable to independently realize their full potential value. Ligand’s strong research and business development capabilities, coupled with its solid financial position and its commitment to additional research and development funding as part of this transaction, gives Metabasis’ portfolio of programs the potential to deliver significant future value to Metabasis’ stockholders."

Highlights of the Proposed Transaction

— Under the terms of the agreement, Ligand will pay at the closing of the
transaction approximately $3.2 million in cash, less Metabasis’
estimated net liabilities at closing (currently estimated to then be
over $1.3 million) and less an amount deposited in the stockholders’
representative’s fund. At this time, Metabasis estimates the net cash
that will be available for distribution to stockholders of Metabasis at
closing will be approximately $1.8 million.

— In addition to cash, Metabasis stockholders will receive tradable
Contingent Value Rights (one of each series of CVRs (or 4 in total), for
each former Metabasis share) that may result in additional cash payments
to the CVR holders including the following:

o Approximately two-thirds of any milestone payments, royalties or
saleback proceeds collected from Metabasis’ partnership with Roche for
the development of treatments for hepatitis;

o 50% of any net proceeds received for licensing or selling Metabasis’
thyroid receptor b program for hyperlipidemia and/or glucagon program
for diabetes for any transaction entered into in the six years
following closing, 40% and 30%, respectively, of any proceeds from
such a transaction entered into in the seventh and eighth years
following closing, and 20% of any proceeds from such a transaction
entered into in the ninth and tenth years following closing;

o 90% of any net proceeds received for licensing or selling Metabasis’
MB07133 program for the treatment of hepatocellular carcinoma for any
transaction entered into in the six months following closing, 30% of
any proceeds from such a transaction entered into after the sixth
month anniversary of closing and before the two year anniversary of
closing, and 10% of any proceeds from such a transaction entered into
in the third through tenth years following closing;

o 60% of any net proceeds from any disposition of Metabasis’ equity
interest in PeriCor Therapeutics, Inc., which in partnership with
Schering-Plough Corporation is in Phase III development of a compound
for the prevention of adverse cardiovascular and cerebrovascular
outcomes in patients undergoing coronary artery bypass graft surgery;

o 50% of any net proceeds received for licensing or selling any of
Metabasis’ other drug development programs or certain platform
technologies for any transaction occurring with respect to any such
program before Ligand has made research and development investments in
excess of a specified amount on such program, and 25% in the event
Ligand’s investments exceed such amount on such program; and

o any shortfall in Ligand’s commitment to spend at least $8 million in
funding Metabasis programs over 42 months following the close of the
transaction.

— Aside from what is due to Metabasis’ CVR holders and subject to certain
obligations, Ligand will retain all rights and economic interests in the
programs and have full control over the development decisions for the
pipeline programs. Ligand has agreed to spend a minimum of $7 million on
Metabasis programs over the 30 months following closing, unless both the
glucagon and TR programs have failed or a major licensing event has
occurred for at least one of those two programs, and to spend a grand
total of $8 million within the 42 months following closing.

— A Metabasis stockholder representative will monitor compliance with
Ligand’s funding obligation and oversee the collection and disbursement
of cash to the CVR holders. A rights agent will be retained to collect
any cash payments due to the CVR holders and will disburse net proceeds,
if any, every six months.

— The transaction is expected to close in early 2010 and is subject to
approval by Metabasis’ stockholders and other customary closing
conditions.

With the acquisition of Metabasis, Ligand does not anticipate any change to its year-end 2009 financial outlook. For 2010, the required cash payment of $3.2 million is projected to be largely offset by the potential receipt of a cash milestone from Roche for the advancement of its program for hepatitis, net of the portion of that payment to be allocated to CVR holders. The obligation for funding Metabasis’ programs is not expected to materially change Ligand’s overall spending over the next several years, as spending for R&D projects can be directed as needed to the highest priority programs.

Metabasis Contributes the Following to Ligand

— Hepatitis Program -Metabasis entered into a fully funded collaboration
and license agreement with Roche in 2008 to develop new treatments for
hepatitis C viral infection utilizing the proprietary HepDirect(R)
liver-targeting technology. The lead HepDirect Nucleoside, MB11362, was
declared a clinical candidate in the second quarter of 2009. Advanced
preclinical development studies are ongoing in preparation for a
first-in-human clinical program. Under the terms of the license
agreement, Roche will fund 100% of the program costs and will make
milestone and royalty payments upon the achievement of certain
development events and commercialization of MB11362 and/or other
applicable HepDirect compounds covered under the agreement. Ligand will
retain approximately one-third of any payments received.

— Glucagon Receptor Antagonist Program – Metabasis has developed
chemically novel, potent, orally bioavailable glucagon antagonists for
treating type 2 diabetes. The lead compound, MB11262, has shown
significant and consistent lowering of blood glucose when dosed orally
in numerous diabetic animal models and is currently in advanced lead
optimization stage. Ligand will retain 50% to 80% of the net proceeds of
any transaction for this program.

— Thyroid Receptor b Agonist Program – Thyroid receptor activation in the
liver affects the expression of several genes, leading to reductions in
LDL, triglycerides and LP(a) while its activation in extra-hepatic
tissues result in dose-limiting side effects. Metabasis has developed a
liver-targeted TRb agonist, MB07811, using HepDirect prodrug technology
and other structural characteristics for the treatment of
hyperlipidemia. Phase I single and multi-dose clinical trials of MB07811
have been completed. In addition, Metabasis has an advanced discovery
program to identify second-generation TR agonists with potential
improvements in the therapeutic index for lowering cholesterol and other
lipids associated with cardiovascular risks. Ligand will retain 50% to
80% of the net proceeds of any transaction for this program.

— MB07133 Program – Metabasis has developed MB07133, a HepDirect prodrug
of the intermediate form of a known oncolytic, which is designed to
deliver high concentration of the active form of the drug for the
treatment of hepatocellular carcinoma. Metabasis has completed a repeat
cycle Phase I/II clinical trial of MB07133. Ligand will retain 10% to
90% of the net proceeds of any transaction for this program.

— PeriCor Therapeutics – Metabasis has a common stock ownership position
in PeriCor Therapeutics, Inc., a private, clinical-stage company focused
on myocardial protection. PeriCor sublicensed rights from Metabasis to
acadesine and three additional Adenosine Regulating Agents in 2005.
PeriCor recently licensed acadesine to Schering-Plough and the compound
is in a Phase III clinical trial for the prevention of adverse
cardiovascular and cerebrovascular outcomes in patients undergoing
coronary artery bypass graft surgery. Ligand will retain 40% of the net
proceeds of any disposition of its PeriCor stock.

— HepDirect Technology: HepDirect technology supplements Ligand’s core
drug discovery technology platform of ligand-dependent gene expression
and ultra-high throughput combinatorial chemistry screening. HepDirect
is a prodrug technology that targets delivery of certain drugs to the
liver by using a proprietary chemical modification that renders a drug
biologically inactive until cleaved by a liver-specific enzyme.
HepDirect may improve efficacy and/or safety of certain drugs and can be
applied to marketed or new drug products. Ligand will retain 50% to 75%
of any net proceeds received for licensing or selling the HepDirect
technology.

— Other Product Candidates and R&D Programs – Metabasis has other product
candidates, including MB07803 for diabetes and pradefovir for hepatitis
B, and early stage R&D programs including glucokinase activators for
diabetes and DGAT-1 inhibitors for obesity. Ligand will retain 50% to
75% of the net proceeds for any deal generated from these programs.

BioSante Pharmaceuticals and Cell Genesys Announce Completion of Merger

On October 14, 2009 BioSante Pharmaceuticals, Inc. (NASDAQ: BPAX) and Cell Genesys, Inc. (NASDAQ: CEGE), reported the successful completion of their previously announced merger of Cell Genesys with and into BioSante, with BioSante as the surviving company, under which BioSante now has acquired all of the outstanding shares of Cell Genesys common stock (Press release, BioSante, OCT 14, 2009, View Source [SID1234531734]).

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BioSante intends to focus primarily on LibiGel, BioSante’s testosterone gel in Phase III clinical development under a U.S. Food and Drug Administration (FDA) agreed Special Protocol Assessment (SPA) for the treatment of female sexual dysfunction (FSD). BioSante also intends to seek future development opportunities for GVAX Immunotherapies including combinations with BioVant, BioSante’s vaccine adjuvant, and possible external collaborations, and also will seek to outlicense other former Cell Genesys technologies. In addition, BioSante now owns a 16 percent equity ownership position in Ceregene, Inc., a former subsidiary of Cell Genesys which is developing gene therapies for neurodegenerative disorders.

"Closing the merger today is a very exciting development for BioSante. We now have accomplished our objective of having enough cash on hand to complete the LibiGel clinical development program to and through submission of a new drug application (NDA) in the first half of 2011," said Stephen M. Simes, president and CEO of BioSante. "The merger follows our successful registered direct financing closed on August 13, 2009 and our recent announcement of continued safety of LibiGel in our Phase III clinical studies. We now will accelerate completion of the LibiGel clinical development program to be in a position to submit the NDA in a timely fashion. We also will work to maximize the value of our newly acquired GVAX immunotherapies."

"The successful closing of our merger with BioSante provides an impressive array of opportunities to create value from the assets of the combined company," said Stephen A. Sherwin, M.D., the former chairman and CEO of Cell Genesys, and as a result of the merger, a new director of BioSante. "I am very pleased to have the opportunity to serve as a director of BioSante and look forward to working with the BioSante team."

The combined company’s ownership composition consists of approximately 62% from BioSante stockholders and 38% from the former Cell Genesys stockholders. BioSante stockholders approved the merger on September 30, 2009, and the former Cell Genesys stockholders approved the merger agreement and the transactions contemplated thereby at a special meeting of stockholders held today. Well over 90 percent of shares voted were voted in favor of the merger. Effective at the close of business today, trading in Cell Genesys common stock will be discontinued. All remaining Cell Genesys employees and management were terminated effective today.

In addition to Dr. Sherwin, John T. Potts, Jr., M.D., a former Cell Genesys director, also now serves as a director of BioSante as a result of the merger. Stephen M. Simes, president and CEO of BioSante, and Phillip B. Donenberg, CFO of BioSante, continue to serve in those positions, and Dr. Louis W. Sullivan, chairman of the board of BioSante, continues in that position.

Pursuant to the merger, the payment obligations of Cell Genesys under its 3.125% convertible senior notes due 2011 and 2013, respectively, were assumed by BioSante. Prior to the merger, the 2011 and 2013 notes were convertible into common stock of Cell Genesys at a conversion price of $9.10 and $0.68, respectively, and upon the merger, pursuant to the indentures governing those notes, the 2011 and 2013 notes became convertible into common stock of BioSante at a conversion price of $49.78 and $3.72, respectively.

About LibiGel

LibiGel is a gel formulation of testosterone designed to be quickly absorbed through the skin after application of a pea-sized dose of gel on the upper arm, delivering testosterone to the bloodstream evenly over time and in a non-invasive and painless manner. Though generally characterized as a male hormone, testosterone also is present in women and its deficiency has been found to decrease libido or sex drive. In addition, studies have shown that testosterone therapy can increase bone density, raise energy levels and improve mood, in addition to boosting sexual desire and activity. According to a study published in the Journal of the American Medical Association, 43 percent of American women (about 40 million) experience some degree of impaired sexual function. Among the more than 1,400 women surveyed, 32 percent lacked interest in sex. According to IMS data, 2.0 million testosterone prescriptions were written off-label for women by U.S. physicians in 2007. The majority of women with FSD are postmenopausal, experiencing FSD due to hormonal changes following menopause, whether natural or surgical.

About GVAX Immunotherapies

GVAX cancer immunotherapies are non patient-specific therapies comprised of whole tumor cells that have been modified to secrete GM-CSF (granulocyte-macrophage colony-stimulating factor), an immune stimulatory cytokine, and then irradiated for safety. GVAX is administered via intradermal injections on an outpatient basis. To date, over 1000 patients have been treated in clinical trials with different GVAX cancer immunotherapies for various types of cancer. Although phase III trials in prostate cancer were discontinued in 2008, phase II trials under physician investigator sponsored-INDs are ongoing at the Sidney Kimmel Cancer Center at Johns Hopkins Hospital in pancreatic cancer, leukemia and breast cancer.

CRT to licence Telomere targeting agents to Pharminox for Drug Development

On October 13, 2009 Cancer Research Technology (CRT) – Cancer Research UK’s development and commercial arm – and the cancer drug discovery company Pharminox Ltd (Pharminox) reported that CRT has granted Pharminox an exclusive worldwide licence over its programme targeting telomeres and telomerase – the enzyme that is responsible for maintaining them (Press release, Cancer Research Technology, OCT 13, 2009, View Source [SID1234523344]).

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Today’s announcement comes only a week after three American researchers were awarded this year’s Nobel Prize for Physiology and Medicine* for their pioneering research into the role of telomeres and telomerase.

Telomeres are the repeat sequences of DNA and associated proteins found at the ends of chromosomes, which act as ‘protective shields’ to maintain chromosomal integrity. In normal cells, these shields get smaller each time a cell divides, until they reach a critically short length at which point the cell stops dividing and ultimately dies. In most cancer cells, however, the part of the telomere lost in cell division is restored by the telomerase enzyme, allowing the cells to continue to divide – effectively rendering them immortal.

Telomerase is thought to be expressed in around 90 per cent of tumours, but telomerase activity is barely detectable in normal tissues – making this enzyme an important target for cancer drug development.

Professor Malcolm Stevens OBE, FRS from the University of Nottingham, who led the original research programme, and who will continue to be involved in the project in his role as chief scientific officer at Pharminox, said: "Telomeres act in the same way as the little plastic caps on the ends of our shoelaces, protecting our chromosomes from fraying. The compounds that we have discovered appear to have a dual mechanism of action: they not only prevent telomerase from replacing the telomeric DNA lost in cell division, but they are also able to disrupt the protective cap around the telomere itself, thereby inducing cell damage and exerting a more rapid anti-tumour effect.

"The programme has made considerable progress and we have already seen promising anti-tumour activity in preclinical tests, but there is still some way to go before compounds from the programme could be used as new cancer treatments."

Peter Worrall, chief executive officer of Pharminox, added: "The critical role of telomeres and telomerase in protecting and immortalising cancer cells makes this a fundamentally important area of cancer science to explore. Today’s agreement with CRT is exciting for Pharminox, and will allow us to continue our work to discover and develop potent and selective telomere targeting agents that could one day offer a new approach to the treatment of cancer."

Dr Phil L’Huillier, CRT’s director of business management said: "We are delighted to be entering into this agreement with Pharminox and are confident that these compounds have strong development potential, thanks to the extensive investigation and development work undertaken by several teams of scientists from across the UK and Europe including the contribution of the CRT’s own Discovery Laboratories, and more recently by Pharminox itself. Pharminox is in an excellent position to take forward this research in the hope of finding effective new treatments which have the potential to treat many forms of cancer."

Under the terms of the agreement, CRT will receive an undisclosed upfront payment and will be eligible for milestone payments as well as royalties on net sales of any resulting treatments. Upfront payment, milestones and royalties will be shared between CRT, the University of Nottingham – where the research programme funded by Cancer Research UK originates from – and The Institute of Cancer Research, whose scientists also contributed to the research.

Santhera Reports Closing of Juvantia Acquisition and Final Upfront Payment from Partner Biovail

On October 5, 2009 Santhera Pharmaceuticals (SIX: SANN), a Swiss specialty pharmaceutical company focused on orphan neuromuscular diseases, reported the final closing of the acquisition of Oy Juvantia Pharma Ltd of Turku, Finland (Press release, Santhera Pharmaceuticals, OCT 5, 2009, View Source;id=196741 [SID1234523622]). Santhera issued 105,973 previously reserved shares from its authorized share capital to Juvantia investors, as announced when exercising its option to acquire Juvantia on August 17, 2009. The closing of the transaction triggers a final upfront payment of USD 4 million from Biovail Laboratories International SRL , a sububsidiary of Biovail Corporation, Santhera’s licensing partner for the further development and marketing of JP-1730/fipamezole to treat Dyskinesia in Parkinson’s Disease in the United States and Canada.

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The new shares issued to the former Juvantia shareholders as a consideration for their sale of Juvantia to Santhera will be listed on the SIX Swiss Exchange today. Upon this transaction, the share capital of Santhera Pharmaceuticals Holding AG will consist of 3,629,266 listed shares with a nominal value of CHF 1 each. The available amount of authorized share capital will be reduced accordingly by CHF 105,973 to CHF 323,945.

In August 2009, Biovail acquired the US and Canadian rights to develop and commercialize JP1730/fiapmezole for the treatment of levodopa -induced Dyskinesia in Parkinson’s Disease. Under the terms of the agreement Santhera received a partial upfront payment of USD 8 million and is entitled to up to USD 180 million in development and commercialization milestones and royalties of 8 to 15% on future net sales. Following the closing of the acquisition of Juvantia, Santhera is now entitled to a final upfront payment from Biovail in the amount of USD 4 million.

Upon application by Santhera Pharmaceuticals Holding AG, the Regulatory Board of the SIX Swiss Exchange granted an exemption from the obligation to produce a prospectus in connection with the listing of 105,973 newly issued shares

Exemption from the obligation to produce a listing prospectus was granted upon analysis of the overall situation of the listing of new shares in connection with the acquisition of Juvantia. In particular, the Regulatory Board decided to grant this exemption due to the fact that the collaboration with Juvantia and the option agreement with former shareholders of Juvantia defining the terms and conditions for the potential acquisition of Juvantia were already fully disclosed in the offering memorandum and listing prospectus of the IPO of Santhera back in 2006.

Also, importantly, in order to comply with requirements regarding ad-hoc publicity, contractual arrangements between Santhera and Juvantia required Santhera to disclose important activities and developments of Juvantia. In addition and in contrast to other capital increases in connection with acquisitions, due to the fact that the target company Juvantia has been known for several years, the need for information of investors and market participants was less.

Moreover, since Santhera’s IPO, all annual reports contained relevant information about the potential acquisition of Juvantia. In particular also the maximum number of the newly to be issued shares from authorized capital upon exercising the option for the acquisition were disclosed.

The Regulatory Board appreciated in its analysis the small size of the capital increase of approximately 3% as well as the fact that the acquisition does not lead to a structural change requiring publication of additional financial information in a listing prospectus (financial information on Juvantia and pro-forma consolidated financial information) and also that the shares were placed with the former shareholders of Juvantia. The Regulatory Board notes however that these last-mentioned facts alone would not have lead to an exemption from the obligation to produce a listing prospectus.