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New Data on MAGE-A3 Cancer Immunotherapy Support Potential Novel Options of Treating Non-Small Cell Lung Cancer and Melanoma

Gene Expression Profiling of Tumor is Correlated With Clinical Response

CHICAGO, May 30, 2008 /PRNewswire-FirstCall/ -- New data presented by GlaxoSmithKline (GSK) today highlighted the potential of its investigational MAGE-A3 Antigen-Specific Cancer Immunotherapeutic (ASCI) through results of three studies evaluating highly targeted immunotherapy as a treatment for metastatic melanoma and non-small cell lung cancer (NSCLC). These data were presented at the 2008 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract Nos: 9065(1), 9045(2) and 7501(3)).

A randomized, open label Phase II study designed to evaluate two different formulations of the MAGE-A3 ASCI in patients with metastatic melanoma has been conducted. In this study, the ASCI, which is a combination of MAGE-A3 recombinant protein and a GSK proprietary Adjuvant System, was evaluated and resultant data suggest a positive trend for clinical response. These data also demonstrate the induction of a desirable immune response, including humoral and cellular responses. These study results represent a second positive trend for clinical activity for the novel MAGE-A3 cancer immunotherapeutic, following encouraging clinical results reported in a separate double-blind, placebo-controlled Phase II study of patients with NSCLC(4). The encouraging results from the Phase II NSCLC study have led to a Phase III safety and efficacy trial in MAGE-A3-positive NSCLC patients (stage IB, II and IIIA) who have undergone complete surgical resection (MAGRIT; MAGE-A3 Adjuvant Non-Small Cell LunG CanceR ImmunoTherapy).

At this year's ASCO, GSK also presented data regarding the use of the genetic profiling of melanoma in predicting clinical outcomes of treatment with MAGE-A3 ASCI. Biopsies performed on the melanoma tumors prior to immunization were used to identify genetic markers expressed by the disease. These markers enabled researchers to establish a correlation between the expression of given genes and the clinical response induced by the MAGE-A3 ASCI in metastatic melanoma(2).

In addition, GSK presented data on the genetic profiling of patients with NSCLC. In a retrospective analysis, a predictive gene signature similar to that observed in melanoma was associated with a lower rate of disease recurrence in the MAGE-A3 treated group(3).

"These phase II data mark another significant milestone for the development of the MAGE-A3 ASCI as a potential novel cancer therapy. Validation of a predictive gene signature, combined with selection of patients who express cancer antigens of interest, may allow GSK to improve predictions of a patient's clinical response to treatment with cancer immunotherapeutics," said Johan Vansteenkiste, Professor of Internal Medicine, Faculty of Medicine, . "They also provide further positive proof-of-concept Phase II data which highlight the importance of the ongoing MAGRIT Phase III trial in Non-Small Cell Lung Cancer."

Phase II Melanoma Data: abstract # 9065(1)

A randomized, open-label Phase II study designed to evaluate MAGE-A3 recombinant protein combined with two different Adjuvant Systems was conducted. A total of 72 patients with measurable metastatic MAGE-A3-positive cutaneous melanoma (unresectable or in transit stage III or stage IV M1a) were randomized to receive immunization with MAGE-A3 protein combined with either AS15 or AS02B as first-line metastatic treatment. Patients were to receive a maximum of 24 immunizations over four years. Clinical activity is assessed by the RECIST criteria, the international standards for evaluation of solid tumors. Complete response (CR) and partial response (PR) i.e, disappearance or significant reduction of tumor, were reported in four patients in the AS15 group (3 CR and 1 PR) with two of these ongoing for more than two years; in the AS02B arm, one patient showed a partial response which lasted for 6 months.1 The safety profile was similar in both groups with the majority of reported adverse events being mild or moderate local or systemic reactions(1).

Gene Profiling in Melanoma: abstract # 9045(2)

Gene expression profiling by microarrays was used to identify markers predictive of the clinical activity of the MAGE-A3 ASCI recorded in the phase II melanoma study. Gene expression profiling was performed on tumor biopsies taken prior to any immunization, leading to the identification of a gene signature which reflects a specific immune micro-environment present prior to any therapeutic intervention. This gene signature seems to be strongly associated with MAGE-A3-induced clinical responses(2).

Gene Profiling in Non-Small Cell Lung Cancer: abstract # 7501(3)

These data show that it may be possible to identify patients that present a high or low risk of relapse after surgery. A gene signature similar to that observed in melanoma was associated in a retrospective analysis with a lower rate of disease recurrence in the MAGE-A3 treated group. Another signature that is predictive to clinical activity of the MAGE-3 ASCI treatment, which increased clinical activity by a factor of 2, was also described(3).

This specific set of data follows the proof of concept Phase II data that GSK reported at ASCO in 2007, which showed a 27% reduction in the relative risk of NSCLC recurrence following surgery in patients treated with the MAGE-A3 ASCI, compared to placebo(4). In the patients population selected for the presence of the predictive gene signature, a 43% reduction in the relative risk of relapse was observed(3). (Data on file).

Based on these encouraging data in NSCLC, GSK has initiated patient recruitment to a randomized and controlled Phase III efficacy and safety trial (MAGRIT) for this novel cancer immunotherapy. MAGE-A3 ASCI will be evaluated as adjuvant therapy in about 2,270 MAGE-A3-positive patients with completely resected stage IB, II or IIIA NSCLC in the large MAGRIT trial. The gene profiling data presented at ASCO will be further validated during the ongoing NSCLC MAGRIT Phase III trial.

"This is an exciting time to be amongst those at the forefront of cancer immunotherapy research," said Dr. Vincent Brichard, Vice-President, Head of Cancer Immunotherapeutics at GSK Biologicals. "These data presented today and the launch of the large MAGRIT trial are indicative of GSK's ongoing commitment to researching new ways of treating cancer and focus on developing the right medicine tailored to identify the patients most likely to benefit from it. We are keenly anticipating the results of the Phase III trial and what it may mean for the future of cancer treatment."

About ASCIs and MAGE-A3 ASCI

GSK's ASCIs represent a novel class of medicines designed to train the immune system to recognize and eliminate cancer cells in a highly specific manner. These novel cancer immunotherapeutics combine tumor antigens, delivered as purified recombinant proteins, and GSK's proprietary Adjuvant Systems which are specific combinations of immunostimulating compounds selected to increase the anti-tumor immune response. ASCIs will be investigated to support their use to reduce the risk of tumor recurrence following surgery, or to impact tumor growth in an early metastatic setting.

The highly specific mode of action of GSK's ASCIs may not only avoid harming the normal tissue but also aid in selecting patients eligible for the treatment, depending on the expression of the tumor antigens.

MAGE-A3 is a tumor-specific antigen that is expressed in a large variety of cancers, including Melanoma, Non-Small Cell Lung Cancer, Head and Neck Cancer, Bladder Cancer, with no expression in normal cells. Expression of the MAGE-A3 gene has been observed in testicular cells but without antigen presentation capabilities.

MAGE-A3 protein has been in-licensed by GSK from the Ludwig Institute for Cancer Research, the largest international academic institute dedicated to understanding and controlling cancer. MAGE-A3 ASCI is an investigational compound and it is not approved for use in any indication in any country at this time.

About melanoma

Melanoma is a type of cancer which develops when melanocytes (pigment cells in the skin) become malignant and start to grow and divide at an abnormally quick pace, spreading into the surrounding surface layers of skin. According to the World Health Organization (WHO), two to three million non-melanoma skin cancers and 132,000 melanoma skin cancers occur globally each year.(5)

About non-small cell lung cancer

According to the Global Lung Cancer Coalition, more than 1.2 million new cases of lung cancer are diagnosed each year worldwide, and approximately 1.1 million deaths occur annually around the world.(6)

About GlaxoSmithKline and GlaxoSmithKline Biologicals

GSK Biologicals (GSK Bio), one of the world's leading vaccine manufacturers, is headquartered in Rixensart, Belgium, where the majority of GlaxoSmithKline's activities in the field of vaccine research, development and production are conducted. GSK Bio employs more than 1,500 scientists, who are devoted to discovering new vaccines and developing more cost-effective and convenient combination products to prevent infections that cause serious medical problems worldwide. GSK Bio is also developing innovative immunotherapy compounds to treat cancer patients.

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For company information please visit http://www.gsk.com.

Cautionary statement regarding forward-looking statements

Under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, the company cautions investors that any forward-looking statements or projections made by the company, including those made in this Announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group's operations are described under 'Risk Factors' in the `Business Review' in the company's Annual Report on Form 20-F for 2007.

References:

(1) Kruit W, Suciu S, Dreno B, et al `Immunization with recombinant MAGE-A3 protein combined with adjuvant systems AS15 or AS02B in patients with unresectable and progressive metastatic cutaneous melanoma: a randomized open-label phase II study of the EORTC Melanoma Group J Clin Oncol 26: 2008 (May 20 suppl; abstr 9065).

(2) Louahed J, Gruselle O, Gaulis S et al `Expression of defined genes by identified by pre-treatment tumor profiling: association with clinical responses to the GSK MAGE-A3 immunotherapuetic in metastatic melanoma patients, J Clin Oncol 26: 2008 (May 20 suppl; abstr 9045).

(3) Vansteenkiste J, Zielinski M, Linder A et al `Association of gene expression signature and clinical efficacy of MAGE-A3 antigen-specific cancer immunotherapeutic (ASCI) as adjuvant therapy in resected stage IB/II non-small cell lung cancer (NSCLC)' J Clin Oncol 26: 2008 (May 20 suppl; abstr 7501).

(4) Vansteenkiste J, Zielinski M, Linder A et al `Final results of a multi-center, double-blind, randomized, placebocontrolled Phase II study to assess the efficacy of MAGE-A3 immunotherapeutic as adjuvant therapy in stage IB/II Non-Small Cell Lung Cancer (NSCLC)' Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 7554.

(5) http://www.who.int/uv/faq/skincancer/en/index1.html (Date of access: May 6, 2008).

(6)

http://www.lungcancercoalition.org/files/File/90280%20GLCC%20English.pdf - (Date of access May 2008).

CONTACT: For on-site contact at ASCO May 30 - June 3, 2008: U.S mediaonly: Sarah Alspach - +1-215-287-6354, Global media: Garry Daniels -+32-4758-05140 / +32-4770-31613; Inquiries: US Media inquiries: Mary AnneRhyne, +1-919-483-2839; UK Media inquiries: Philip Thomson,+44-20-8047-5502, Gwenan White, +44-20-8047-5502, Alice Hunt,+44-20-8047-5502; European Analyst/Investor inquiries: David Mawdsley,+44-20-8047-5564, Sally Ferguson, +44-20-8047-5543, Gary Davies,+44-20-8047-5503; US Analyst/ Investor inquiries: Frank Murdolo,+1-215-751-7002, Tom Curry, +1-215-751-5419

Ticker Symbol: (:GSK),(:GSK.P),(:GSKY),(:GSK),(:GSK.F)

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Posted: May 2008

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