Deal struck for new investigational anti-cancer drug to target leukaemia and lymphoma

On January 4, 2010 CANCER RESEARCH UK and Cancer Research Technology (CRT), the charity’s development and commercialisation arm, reported to undertake a phase I clinical trial of an investigational monoclonal antibody * drug from Merck KGaA, Darmstadt, Germany, called DI-B4 (Press release, Cancer Research Technology, JAN 4, 2010, View Source [SID1234523342]).

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DI-B4 is the fourth anti-cancer drug to enter Cancer Research UK’s Clinical Development Partnerships (CDP) programme** – an initiative which allows companies to retain the rights to a treatment whilst enabling the charity to take on its early development work. DI-B4 is the first monoclonal antibody to join the scheme.

DI-B4 binds to the CD19 protein, found on B-cells, and is thought to recruit cells from the immune system to attack the tumour. It is hoped that it may one day help patients with leukaemia and lymphoma who do not respond to existing therapies. Currently, the standard treatment for B-cell lymphoma targets the CD20 protein.

DI-B4 will be one of the first drugs to be manufactured at Cancer Research UK’s new state-of-the-art, £20 million Biotherapeutic Development Unit***. After pre-clinical work on it has been completed, it will be taken into a phase I trial in around 20-40 patients with advanced B-cell lymphoma – a cancer of the white blood cell.

The trial will be managed by Cancer Research UK’s Drug Development Office and will take place at up to five**** hospitals across the UK.

Under the terms of the partnership, Cancer Research UK will fund the study through early clinical development. Merck KGaA will then have an option to take forward and commercialise the drug in exchange for future payments to the charity. If Merck KGaA elects not to progress the programme, the rights to the molecule will be given to CRT to secure an alternative development partner.

Dr Nigel Blackburn, director of Cancer Research UK’s Drug Development Office, said: "We’re very excited to be entering this venture with Merck KGaA. Equipped with the knowledge they have gained from creating the antibody, we will use our brand new manufacturing facility to develop it into a potential new treatment for cancer patients."

Dr Keith Blundy, chief executive of CRT said: "In an increasingly competitive market place, pharmaceutical and biotechnology companies have to focus strategically on certain areas of research and hold back on others. This deal demonstrates how we can work together to progress cancer drugs."

Dr Andrew Davies, Cancer Research UK senior lecturer in medical oncology at University of Southampton, who will run the phase I trial at Southampton General Hospital, added: "Existing treatments which target cancerous cells and draw in the body’s immune system can be extremely helpful. But we still need to search for alternative approaches for patients with B-cell cancers which have not responded to existing treatments. We hope that DI-B4 will have the same effects in patients as it has shown in the lab."

CRT grants rights for targeting technology to Aura

On December 23, 2009 Cancer Research Technology (CRT) – Cancer Research UK’s commercialisation and development arm – reported it has granted Aura Biosciences Inc. worldwide licence to use its cancer-targeting peptides in delivering cancer treatments directly to the tumour (Press release, Cancer Research Technology, DEC 23, 2009, View Source [SID1234523343]).

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These peptides bind to a protein on the surface of the cell called integrin αγβ6, a protein complex that is found at high levels on many tumour cells but is absent in most normal tissues. By seeking out this protein and binding to it, the peptides are able to deliver cancer treatments directly to the site with increased precision and reduced side effects. One of the cancers this could have particular benefit in targeting is pancreatic cancer as these tumours express high levels of integrin αγβ6. Pancreatic cancer is currently very difficult to treat with only around 2 to 3 per cent of patients surviving the disease for five years or more. Recent pre-clinical studies have also shown that these peptides may improve imaging in pancreatic cancer by binding to the αγβ6 *.

This deal strengthens Aura’s investment in the technology and builds on an evaluation agreement between Aura and CRT announced earlier this year**. The peptides were originally developed at Queen Mary, University of London with support from Cancer Research UK and DebRA – who work on behalf of people in the UK with the genetic skin blistering condition Epidermolysis Bullosa (EB).

Under the terms of the agreement, Aura Biosciences will make an upfront payment to CRT as well as providing clinical development milestones and royalties on future sales. Aura will exclusively fund the development work, and have sub-licensing rights on agreed terms.

Dr Elisabet de los Pinos, chief executive of Aura Biosciences said: "This partnership with CRT enables us to make use of their peptide technology as way to deliver our innovative NanosmartTM treatment particles – which are hollow particles made of nano-sized protein shells – to the tumour with increased accuracy. We are delighted with the progress we have already made in developing the technology and are looking forward to progressing it into potential new treatments for cancer."

Dr Phil L’Huillier, CRT’s director of business management said: "These peptides – combined with Aura’s award winning nanotechnology – have the potential to seek out and destroy cancer cells, leaving the surrounding areas unharmed. We believe this technology could have particular strengths in delivering treatments for cancers that have limited treatment options such as pancreatic and head and neck cancer. Crucially this targeted treatment could also reduce the side effects that are commonly associated with standard therapies. We look forward to the results of the programme with great interest."

Cosmo Pharmaceuticals offers to acquire BioXell

On November 18, 2009 Cosmo Pharmaceuticals S.p.A. (SIX Swiss Exchange: COPN) reported its intention to launch a public tender offer to acquire all outstanding shares of BioXell S.p.A. (SIX Swiss Exchange: BXLN) (Press release, Cosmo Pharmaceuticals, NOV 18, 2009, View Source [SID:1234510964]). Simultaneously with this announcement, Cosmo has published a pre-announcement stipulating in detail the terms and conditions of its offer, the principal elements of which are as follows:

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A total purchase price of up to CHF 41.3 million (€ 27.4 million), for 100% of BioXell’s outstanding share capital, consisting of

CHF 15.1 million in cash;
1’132’500 of newly issued Cosmo shares each with a par-value of EUR 0.25 each; and

1’132’500 options each giving the holder the right to put the Cosmo shares to Cosmo at a strike price of CHF 21.00 between July 1, 2011 and 31 December 2011.

Based upon 5’381’577 registered BioXell shares outstanding, Cosmo’s offer is equivalent to CHF 7.68 per BioXell share, equalling:

CHF 2.8059 in cash,

CHF 3.64 equivalent to 0.21044 newly issued, freely exchangeable Cosmo shares (using Cosmo’s 60-day volume-weighted average closing price), and

CHF 1.23 equivalent to 0.21044 in newly issued put options for Cosmo shares, using typical valuation methods for option pricing.

A premium of 17.1% over BioXell’s volume-weighted average closing share price over the last 60 trading days.

The cash component of the offer will be increased, subject to certain conditions, based on the collection by BioXell of certain receivables or sales (if any should occur) of BioXell’s technology assets to third parties prior to closing of the Offer.

Closing of the offer will be subject to Cosmo having received acceptances representing 60% of BioXell’s outstanding share capital and to Cosmo and to certain other conditions. Cosmo’s majority shareholder, Cosmo Holding SpA, has already given its support for the offer and committed to vote in favour of the required capital increase at a shareholders meeting to be convened in December 2009.

More details of Cosmo’s proposal can be found in the pre-announcement published today. Cosmo expects to launch the offer in December. Closing of the offer is expected by the end of March 2010.

Mauro Ajani, CEO of Cosmo, commented: "Our offer represents an opportunity to increase our free float and our cash reserves faster and at competitive terms. If 100% of BioXell shares are tendered, our free float will increase by 22% to 32% improving the liquidity of our shares. Whilst we have a comfortable cash position and are profitable, the additional cash will enable us to accelerate a number of our clinical programs and put us in a stronger position to negotiate favourable terms for our un-partnered pipeline products. We look forward welcoming BioXell’s shareholders and are very pleased to offer them the opportunity to participate in the future growth of our company."

BioXell’s board of directors has simultaneously announced today their unanimous support in favour of the proposed transaction with Cosmo and will recommend to its shareholders to accept the tender offer by Cosmo. In addition, Index Ventures and TVM Capital, who together own 19.7% in BioXell, have given undertakings to tender their shares into Cosmo’s offer.

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.