search
for
 About Bioline  All Journals  Testimonials  Membership  News


Australasian Biotechnology (backfiles)
AusBiotech
ISSN: 1036-7128
Vol. 6, Num. 4, 1996
Australasian Biotechnology,
Volume 6 Number 4, July/August 1996,pp.223-229

Peptide Technology Ltd


Code Number: AU96008
Size of Files:
    Text: 26.3K
    Graphics: Photographs (jpg) - 160.5K

Ms Eunice Farram prepared this profile of Peptide Technology Ltd especially for "Australasian Biotechnology". We plan to profile other major Australian biotechnology companies in coming issues. We thank staff of Peptide Technology for their assistance in the preparation of this profile. Photographs were provided by the company.

Peptide Technology Limited is the parent company of the Peptech Group which consists of Peptech (Australia), Peptech (UK), Peptech Animal Health and Cambridge Antibody Technology (CAT, UK). The head office is situated at Dee Why on Sydney's northern beaches. The group has a staff of approximately 120 world wide, with 35 in Sydney. The group's focus is the development, manufacture and marketing of therapeutic drugs for human and animal health care. These products are based on peptides and antibodies which modulate the immune response in the treatment of cancer, inflammation and infectious diseases.

Peptech was established as a public company in Sydney in 1985, by CSIRO scientist Dr. Geoffrey Grigg and associates. Its largest shareholder is a Danish company L nmodtagernes Dyrtidsfond which owns 11.2% of shares. The Peptech group has several links with research institutions in Australia and overseas, including the CSIRO, the Medical Research Council (UK) and the Shemyakin and Immunology Institutes in Russia. The company's R and D staff of 25 in Sydney also provides key support in the development of potential commercial products, financed by R and D syndicates.

Restructuring

Peptech has recently been restructured as part of the company's plan to focus on its proprietary products and reduce expenditure. In 1995 Dr. Roger Aston was appointed chief executive officer of both Peptech and CAT, to oversee this restructuring. Dr. Aston said that the Group would concentrate on products which would yield revenue in the next few years. It would also focus on the development of new products and proceed through drug registrations in the human pharmaceutical field in association with partners. This has already occurred through agreements between CAT and several strategic alliances.

As a result of the restructuring process, Peptech (USA) is no longer trading, and due to losses, Peptech's Danish interests (formerly Peptech Europe), were sold to a Swedish company, Ferring, in May this year. Ferring will lease the existing manufacturing plant which is owned by the Peptech Group. Peptech is seeking secondary listing on the London Stock Exchange, and in preparation for this, now wholly owns Peptech (UK). Its ownership of CAT has now been reduced to 30.6%, to allow CAT to list separately on the London Stock Exchange expected at the end of 1997. The Peptech-CAT relationship will continue to give Peptech access to important technology for the development of new products as well as a share of future profits. Peptech's accounting practices have been modified to accord with current international standards. As a result, there was an approximate AUD 56 million write off of R and D expenditure in 1995, and only R and D costs of projects which are close to commercialisation are now capitalised. It is expected that this procedure will enhance future profits when products are marketed. The half yearly report for 6 months to end of March 1996, showed sales and income increased 16% to nearly $10 million, although there was an operating loss of $10,000. More than half the revenue was from Australia.

Infection and Inflammation Products

GMDP

Peptech has concentrated on projects in the infection and inflammation area. This is reflected in its major product, an immunomodulator which is an analogue of muramyl dipeptide. Glucosaminyl-muramyl-dipeptide (GMDP, N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-isoglutamine, MW 695) was originally developed in the 1970s at the Shemyakin Institute for Bio-organic Chemistry in Moscow. Muramyl dipeptides are the smallest, biologically active components of bacterial cell walls, and they stimulate the immune response by a dual action. GMDP activates macrophages to release cytokines and colony stimulating factors (CSFs). These factors stimulate the differentiation of hemopoietic cells and they also stimulate macrophages and neutrophils to clear infections.

GMDP has a different mode of action from the granulocyte colony stimulating factors (G-CSFs) Filgrastim (marketed by AMGEN under the trade name NEUPOGEN^R), and Lenograstim (the glycosylated form, marketed by AMRAD under the trade name GRANOCYTE^R). These G-CSFs also reduce infection but act by selectively stimulating the maturation of neutrophils from precursor cells in the bone marrow. An advantage of GMDP is that because of its small protein component and acid resistance, it is orally active and can be administered in tablet form, while G-CSFs have to be administered by injection. In addition, GMDP is considerably cheaper than G-CSFs, and may be more appropriate for less severely ill patients. Laboratory tests are currently being carried out to compare GMDP and Filgrastim.

GMDP was initially isolated as a hydrolytic fragment of bacterial cell wall and is prepared by a semi-synthetic route. The disaccharide is produced from fermentation of Micrococcus, and the dipeptide is then produced by peptide synthetic methods. GMDP was initially used in Russia for the treatment and prevention of surgery -related infections. It has undergone clinical and toxicology tests, and was registered in Russia in 1995 (trade name Likopid^R ) for the treatment of psoriasis and other conditions including infections. Psoriasis is an auto-immune, chronic inflammatory disease causing epidermal thickening and scaling skin. It affects about 2% of the population in developed countries. Although it is uncertain how GMDP works in psoriasis, high oral doses of the drug are anti-inflammatory and its efficacy has been confirmed by Phase II trials in Russia. This was shown by substantial patient improvement without rapid relapse after drug withdrawal. Peptech (UK) is involved in the commercialisation and sale of GMDP in Russia.

In 1995 Peptech signed an agreement with Allergan, Inc. (USA) to license GMDP for the treatment of psoriasis, and with the option to fund further developmental work. Under this agreement, Peptech (UK) will perform clinical trials in the UK in collaboration with Allergan. Preliminary studies conducted in Manchester and Wales this year to test the efficacy of GMDP in the treatment of psoriasis, have confirmed the Russian results. Dr. Philip Ledger (Peptech UK) said that the UK results gave the company the confidence to proceed in developing GMDP for the estimated US$500 million psoriasis market. Allergan will also investigate GMDP's potential use in opthalmologic infections caused by herpes virus.

Another application of GMDP is in the treatment of neutropenia which results from cancer chemotherapy. GMDP-stimulated release of CSFs, modulates the proliferation and differentiation of immune cells including macrophages and neutrophils from the bone marrow. This reduces infection and allows higher doses of chemotherapy drugs to be used. Phase I studies have confirmed neutrophil stimulation without adverse side effects. Phase II trials are underway in Australia at four centres involving breast cancer patients, and some results are expected by the end of the year. GMDP's application in the reduction of neutropenia has been excluded from Peptech's option/licence agreement with Allergan. Peptech has obtained patents for GMDP in the US, Japan and some European countries, and patent applications for other novel uses of GMDP have also been filed. The company envisages that GMDP will have routine clinical application by 2001.

Novel Peptides (PTL 78419)

Peptech has developed some novel peptides in its Sydney laboratories. One of them is PTL 78419 designed as an analogue of a portion of the macrophage-derived cytokine Tumour Necrosis Factor (TNF). TNF plays a central role in the mediation of immune activity, including the stimulation of effector cells to act against microorganisms and enhancement of phagocytosis. It is also cytotoxic for tumour cells and acts via cell surface receptors p55 and p75. Elevated TNF levels however, are toxic, and can cause some symptoms of septic shock and blood clotting. Consequently these adverse effects have prevented TNF's clinical application. The 11-amino acid peptide PTL 78419 was selected for its anti-microbial activity, as it activates neutrophils and macrophages leading to the production of oxygen radicals. In vitro and in vivo experimental models confirmed that PTL 78419 was antibacterial, and preliminary results also indicate that the peptide is anti-fungal and anti-viral. Peptech believes that PTL 78419 has potential applications in the treatment of opportunistic infections in immunocompromised patients, as well as an adjunct to antibiotic treatment in diseases such as tuberculosis. It will be undergoing Phase I trials involving severely infected hospital patients, and world wide patents have been granted for PTL 78419 and other TNF agonist peptides.

Carnosine

Another Peptech product developed in conjunction with the CSIRO, is the naturally occurring dipeptide carnosine (b-alanalyl-L-histidine), which may have therapeutic applications in age-related degenerative problems. Carnosine is found at levels up to 20 mM in skeletal muscle and 5mM in the brain, as it is resistant to proteolytic cleavage. Although its precise role in vivo is uncertain, carnosine appears to act as an anti-oxidant by decreasing oxygen free radical-mediated damage either by chelating divalent cations or by scavenging hydroxyl radicals through its imidazole moiety, thus protecting the body against chemical damage. Carnosine has also been found to reduce cross-linking in collagen by prolonging the lifespan of skin fibroblasts and also revitalises cells advanced towards senescence. The product has been licensed to manufacturers for use in cosmetics and as a food supplement.

Carnosine also has the ability to inhibit glycation. Glycation is non-enzymatic glycosylation (the Maillard reaction which causes food browning) in which the reaction of amino groups with sugar aldehyde or keto groups results in cross-linking and the formation of advanced glycosylation end products. The epsilon amino groups of lysine residues in proximity to histidine groups are primary glycation sites, and this sequence is similar to that of carnosine. This indicates that the dipeptide can compete for glycation sites and act as an inhibitor by blocking glycation. Glycation is important in aging and pathological conditions and may result in protein damage. In diabetes, elevated sugar levels lead to a higher rate of toxic glycated proteins resulting in connective tissue damage including cataract formation, renal failure and atherosclerosis. Similarly, in Alzeheimer's disease, glycated -amyloid proteins are found in plaques in the brain which lead to loss of neurones. Carnosine may have a role to play in the inhibition of glycation in these diseases, and Peptech is collaborating with local research groups to examine the development and therapeutic application of carnosine in the various diseases.

Peptide Antagonists

A current collaborative project between Peptech and the Imperial Cancer Research Fund (ICRF, UK) has reached the clinical stage. ICRF has been studying neuropeptides which attach to tumour cell surface receptors and promote tumour growth. Peptide antagonists which bind to tumour cell surface and thus block the activity of growth factors such as substance P, vasopressin and bombesin have been tested in cell culture and tumour models. The peptide antagonists will be tested on patients with small cell lung carcinoma, an aggressive tumour resistant to conventional therapy and responsible for about 100,000 deaths a year world wide. Peptech has been working with the ICRF to synthesise improved "second generation" candidate peptides with greater stability and effectiveness, and holds the option for their commercial development. Dr. Merilyn Sleigh, Peptech's Director of Pharmaceutical Business, said that ICRF's novel approach had significant commercial potential.

Dr. Sleigh discussed some potential future products of the company. A joint project with the Women's and Children's Hospital in Adelaide and the Australian National University, is the development of anti-inflammatory drugs. These are modified polyunsaturated fatty acid (PUFA) molecules which act as anti-inflammatory agents by inhibiting the metabolism of the inflammatory mediator arachidonic acid. The mechanism of reducing inflammation and suppression of cytokine production by PUFA is being investigated, and the treatment of asthma, eczema and ulcerative colitis are targets of these potential new drugs. Dr. Sleigh said that work carried out so far has already increased specificity and efficacy of the molecules, and some are in the early stages of testing, but a candidate molecule for clinical development is not expected to be selected for some time.

Octapeptide - Peptide T

Another project involves Peptide T, an octapeptide. Its mechanism of action is uncertain, but appears to be anti-inflammatory and it also blocks some TNF activity. Although work on Peptide T in AIDS therapy has been discontinued, it has been found to be effective against inflammation induced by herpes viruses. Peptide T's ability to reduce the recurrence of herpes lesions will be explored and clinically tested. Peptech will continue to seek new projects from academic groups in Australia and overseas. " The development of therapeutic peptides is a specialised art, and Peptech aims to add value to interesting drug leads by improving and testing active peptides", said Dr. Sleigh. She added that Peptech's aim for each project is to look for partners to support further development including manufacture and marketing, once a drug was in Phase II trials,

Animal Health Care Products

Peptech Animal Health is a wholly owned but operationally independent subsidiary of Peptech, involved in the development and commercialisation of animal health care products, focusing on control of reproduction and associated behaviour. Dr. Timothy Trigg, the Managing Director, said that the company plans to develop products based on the Gonadotrophin Releasing Hormone (GnRH), as it is the key hormone in orchestrating fertility in mammals. Dr. Trigg explained that the peptide is unstable in vivo, with a half life of less than 30 minutes. Research is therefore concentrated on the controlled release of this hormone which can result in either increased fertility or contraception. Manipulation of this hormone and its analogues is an important technology as it can be applied in many animal species.

Gonadotrophin Releasing Hormone Analogue

Human chorionic gonadotrophin (hCG) is used to increase the precision in predicting ovulation of mares, by inducing ovulation in 48 hours and therefore allowing efficient management of stallions. Continuous use of hCG is inappropriate, however, because of risks and decreased efficiency. The company's major product Deslorelin, (trade name Ovuplant^R) is an implantable, controlled-release peptide which induces ovulation in mares. The peptide is a 9-amino acid analogue of GnRH which acts on the pituitary gland and directly controls luteinising hormone (LH) and follicle stimulating hormone (FSH). Ovulation in induced by increasing the levels of endogenous FSH and LH. Ovuplant^R has the same effect as hCG without its disadvantages and limitations. It is manufactured in Peptech's Sydney facilities and has been marketed since 1995 in Australia, New Zealand and Canada. Applications for registration in other parts of the world are underway, and Peptech expects annual sales of Ovuplant^R will reach $5 million within a few years of registration in the US. Another registered product is a vaccine against GnRH (trade name Vaxstrate^R), which blocks fertility in female cattle. This has applications where bull control is difficult, such as in outback areas of Australia.

Other Animal Health Products

Peptech Animal Health is carrying out research in other areas of reproductive technology. A mechanism has been invented to provide long term delivery of Deslorelin up to one year. This is being developed to reversibly control fertility in male and female dogs and cats. In addition, the drug delivery technology developed for Deslorelin is being investigated for other applications in fertility management, as it can be applied as vaccines, implants or injectables. There are several potential products based on GnRH, including the control of ovulation in cattle and other species, as well as the delay of reproduction in heifers to improve their reproductive efficiency. Other products are being developed based on anti-GnRH vaccine technology. These are the removal of boar taint in pork caused indirectly by testosterone metabolism, improved beef quality and control of behaviour of mares and stallions in horse racing.

Antibody-Based Therapeutics from CAT

The UK antibody technology company CAT was established in 1990 as a joint venture with Peptech, in collaboration with scientists from the Medical Research Council (UK). The company was set up to exploit the unique antibody engineering technique of "humanising" antibodies, which was pioneered by Dr. Gregory Winter in 1990. The technology is based on building genetic libraries of antibody fragments, from which human antibodies of virtually any specificity can be obtained in vitro without immunisation. The procedure uses an antibody selection technique involving more than 10 million antibody variants, with binding affinities and specificities comparable to monoclonal antibodies. These variants are displayed on bacteriophage. After selection, screening and amplification the antibodies are then isolated and produced by growing the selected phage in bacteria. The advantage of this technology is that even antibodies to toxic substances and self-antigens, not previously available with conventional hybridoma technology, can be produced. Moreover, the speed in obtaining these antibodies and their "human" origin make this technology a powerful tool, and it has major applications for therapeutics, diagnostics and research. The market for antibody-based therapeutics has been predicted to be US$5 billion world wide by the year 2000.

CAT recently entered into a joint venture with Techniclone International Corporation (USA), to develop products for cancer therapy and diagnosis. CAT will use its antibody technology with Techniclone's Tumour Necrosis Technology to produce human monoclonal antibodies to deliver radioactive substances to tumours. The company has also signed a non-exclusive licensing agreement with Pfizer Inc., to give Pfizer access to CAT's phage antibody display and selection technologies. The agreement includes several million dollars upfront payment to CAT, to be followed by future milestone and royalty payments from any commercial product Pfizer generates from this technology. CAT joins Pfizer's network of strategic external alliances, known as PfizerGen, which seeks opportunities for collaboration in genomics.

Future Directions

Ms. Dawn Mills the Financial Controller of Peptech, in discussing some of the problems and prospects of the company, said the company's focus had been changed from manufacturing to core projects concentrating on peptide development. A setback for Peptech has been the discontinuation of work on Peptide T in HIV disease, following disappointing Phase II trial results in the US. The main hurdle for Peptech is envisaged to be obtaining efficacy data and registration of GMDP in Europe and the US. Consequently Ms. Mills does not expect significant profits for Peptech for the next 3 years, but is optimistic that profits of about $50 million a year may be expected after this time. This income would be derived mainly from GMDP and products from animal fertility projects.

Mr. Darryl Mellish, Group Vice President (Administration), is enthusiastic of Peptech's future. He explained that the revised corporate plan developed by the company's board in 1995 which involved restructuring activities, had largely been completed. Mr. Mellish said that the company's most significant news is Peptech's expected listing on the London Stock Exchange by the end of the year. This would provide a new range of investors and scrutineers for the company. In preparation for the listing, in June this year Peptech appointed as its sponsor, Nomura International, a major investment bank with expertise in biotechnology and pharmaceuticals. Nomura International will advise Peptech and help to raise funds for research and to accelerate key projects.

CAPTIONS FOR PHOTOS

    Fig.1. Peptech's Sydney laboratories at Dee Why.

    Fig.2. Dr. Roger Aston, Chief Executive Officer, Peptech Group.

    Fig.3. Mr. Darryl Mellish, Group Vice President (Administration).

    Fig.4. Dr. Merilyn Sleigh, Director of Pharmaceutical Business, Peptech (Australia).

    Fig.5. Dr. Timothy Trigg, Managing Director, Peptech Animal Health.

Board Restructuring

In preparation for its London Stock Exchange listing and in line with the Company's continued restructuring, the Directors of Peptide Technology Limited announced on 17 July the appointment of two new Executive Directors and one Non-Executive Director to the Board.

Mr Anthony Bates, age 57, joins the Board as a Non-Executive Director. Mr Bates was formerly Managing Director of Cyanamid Australia and New Zealand (1987-1995) as well as Chairman of Arthur Webster Pty Ltd (1993-1995). Mr Bates is Chairman of Technico Pty Ltd, Director of the Great Southern Energy Corporation and Asian Pacific Specialty Chemicals Limited.

Mr Darryl Mellish, age 44, has been a senior executive with Peptech for over nine years. He is currently responsible for Peptech's corporate administration and operations and joins the Board as an Executive Director in the same capacity.

Mr Malcolm Darvell, age 34, has been appointed to the Board of the Company as Executive Finance Director. Mr Darvell is a UK resident and will be closely involved in the process of listing Peptech on the London Stock Exchange as well as contributing to the Group's financial planning, drawing upon extensive corporate finance and commercial experience.

Mr Paul Hookway, Chairman of Peptech since October 1995, stated "We are delighted to make these new appointments to significantly strengthen the Board of Peptech in anticipation of the next important phase of the Group's development. During the past few months Peptech has undergone substantial changes aimed towards preparing the Group for a listing on the London Stock Exchange and successful further development of a focussed portfolio of peptide based products."

Dr Roger Aston, Peptech's Chief Executive Officer, has recently relinquished his executive responsibilities in Cambridge Antibody Technology (CAT), in order to devote full attention to the Peptech Group. Dr Aston will continue serving as a Non-Executive Director of CAT, as will Mr Paul Hookway.

Australian Stock Exchange Code for Peptide Technology Limited, "Peptide", is PTD.

Patents Granted

Peptide Technology Limited (Peptech) announced on 24 July that it has received notices of grant for international patents in two of its key projects, providing a significant boost for their commercial value and lowering their risk profile.

The US Patent & Trademark Office has approved grant of a patent on Peptech's proprietary drug GMDP, in the treatment of inflammatory conditions associated with infection.

"This is a significant additional step in protecting Peptech's proprietary position. The patent grant provides strong support for our development program for GMDP in the US and Europe, where infection associated with cancer chemotherapy is a key application. Success with this US filing also strengthens our protection in territories such as Russia, where we are marketing Likopid^R (GMDP) for control of post operative infection" said Dr Roger Aston, CEO of Peptech and a named inventor on the patent.

Peptech also announced the grant of US and European patents on its proprietary peptide drug PTL-78419, which is being developed for use in association with antibiotics in treatment of chronic and intractable infections. The Company has almost completed its preclinical program for this peptide, and clinical trials are expected to commence in 1997.

Copyright 1996 Australian Biotechnology Association Ltd.


The following images related to this document are available:

Photo images

[au96008e.jpg] [au96008b.jpg] [au96008c.jpg] [au96008d.jpg] [au96008a.jpg]
Home Faq Resources Email Bioline
© Bioline International, 1989 - 2024, Site last up-dated on 01-Sep-2022.
Site created and maintained by the Reference Center on Environmental Information, CRIA, Brazil
System hosted by the Google Cloud Platform, GCP, Brazil