John Connolly, chief scientific officer of Tessa Therapeutics, and his team pose in a joint lab of Tessa and the Institute of Molecular and Cell Biology in Singapore, on Thursday, February 23 2017. Picture: Bloomberg
John Connolly, chief scientific officer of Tessa Therapeutics, and his team pose in a joint lab of Tessa and the Institute of Molecular and Cell Biology in Singapore, on Thursday, February 23 2017. Picture: Bloomberg

Hong Kong — A meeting between an immunologist and an oncologist in a Singapore cafe seven years ago may go down as one pivotal moment in the war on cancer.

Over a coffee that turned into lunch, immunologist John Connolly and oncologist Han Chong Toh spent hours discussing ways to better harness the immune system to hunt down and kill malignant cells.

Fast-forward to April 2015, when cancer patients began receiving one of their experimental treatments in what their company says is the largest clinical study of its type in the world.

Their first meeting triggered a years-long partnership leading to Tessa Therapeutics, which is developing novel anticancer therapies that rely on turbo-charging the body’s cancer-killing immune system.

Han Chong Toh, chief medical officer of Tessa Therapeutics and deputy director of Singapore's National Cancer Centre. Picture: Bloomberg
Han Chong Toh, chief medical officer of Tessa Therapeutics and deputy director of Singapore's National Cancer Centre. Picture: Bloomberg

The Singapore-based biotechnology firm has two treatments in patient studies, including one in the final of three stages of trials usually needed for regulatory approval. The company says it is also seeking about $100m in extra funding later this year.

"While we are still in clinical trials for these treatments, based on the results we have seen so far, we are very excited by their potential to treat cancer," said Toh, who is both Tessa’s chief medical officer and deputy director of Singapore’s National Cancer Centre.

Possible initial public offering

Tessa is looking at various funding options, said Andrew Khoo, Tessa’s CEO. A possible initial public offering over the next 12-to-18 months may value Tessa at "well over" $500m, based on comparable listed companies worldwide, according to the company.

The Singapore Cancer Centre is one of more than two dozen sites in five countries that will investigate whether Tessa’s treatment, known as TT10, can prolong survival better than conventional therapy in patients with advanced cancer of the nasopharynx — the area behind the nose and above the soft palate — linked to a viral infection.

The medicine works by a taking a sample of the patient’s blood and separating off the infection-fighting T cells, or cytotoxic lymphocytes, that it contains. These are stimulated in the laboratory with specialised cells to produce virus-specific T cells capable of hunting down and destroying cancer cells that express the protein fragments of the virus on the surface of the tumour. These T cells are multiplied in the lab and given back to the patient in the form of an infusion.

Treating cancer

While surgery, radiotherapy, chemotherapy and targeted drug therapies have each boosted cancer survival over the past two centuries, immunotherapy is an emerging frontier. Revenue from treatments in this field is increasing about 14% a year and will reach $119.4bn globally by 2021, according to MarketsandMarkets, a research organisation in Pune, India.

A research technologist prepares a Tessa Therapeutics virus specific t-cells (VST) infusion for cancer patients as part of a clinical trial, at Singapore’s National Cancer Centre, on February 23 2017. Picture: Bloomberg
A research technologist prepares a Tessa Therapeutics virus specific t-cells (VST) infusion for cancer patients as part of a clinical trial, at Singapore’s National Cancer Centre, on February 23 2017. Picture: Bloomberg

"The aim of immunotherapy in treating cancer is giving the immune system the ability to counter the cancer’s evasive ploys," said Asthika Goonewardene, a senior biotech analyst at Bloomberg Intelligence in New York.

While immunotherapy has shown to be highly effective, the downside is that these individualised medicines require a more complicated process to produce than conventional therapies, Goonewardene said.

Also, there have been rare, serious cases in which the therapy triggered an overzealous immune response. "Think of it as nuking the tumour so aggressively, that the gunk causes your body to go into a state of shock," he said.

The safety profile of Tessa’s virus-specific T cells is one of its "key qualities," said Connolly, now Tessa’s chief scientific officer. No severe toxicity events were observed in the more than 100 patients who had received the company’s T cell infusion, he said.

"Many immune-based therapies such as checkpoint blockade work by amplifying a patient’s pre-existing immune response against their cancer. But in many cancer patients, the cancer has totally escaped the immune system and so there is nothing left to amplify," according to Joe Trapani, head of the cancer immunology program at Melbourne’s Peter MacCallum Cancer Centre.

It is in such patients that engineered T Cell vaccines can be used to "manufacture" an immune response in the lab, said Trapani, who was not commenting specifically on Tessa.

Cancer’s viral cause

Worldwide, 330 patients will be recruited for the phase-three trial of TT10, which Tessa anticipates may lead to the first T-cell therapy for a solid tumour approved by the US Food and Drug Administration. In this case, the treatment is directed at cancer cells harbouring Epstein-Barr virus, a type of herpes virus responsible for infectious mononucleosis or "kissing disease," that lingers in certain white blood cells of an infected person for life.

More than 9 in 10 people are infected worldwide with Epstein-Barr virus. In rare cases, it has been linked to several types of cancer, including Hodgkin lymphoma, Burkitts lymphoma and naso-pharyngeal and stomach cancer.

Epstein-Barr is one of seven human viruses that have been found to cause as many as 15% of cancers. Others include human papillomavirus, which is the main cause of cervical cancer, and the human immunodeficiency virus, which has been linked to Kaposi sarcoma, cervical cancer and certain kinds of non-Hodgkin lymphoma.

Tessa is also testing its TT10 product to tackle gastric cancer in pre-clinical research, and has similar treatments in early-stage trials for cervical cancer and oropharyngeal cancer, which are linked to the human papillomavirus. In the next 18 months, the company aims to complete the phase 3 trial, start one mid-stage and four phase 1 trials, and further invest in core research and development, according to a company presentation in February.

Singapore’s foray

Tessa’s mid-stage study in nasopharyngeal cancer found 63% of patients were still alive after two years. That compared with 43% receiving a four-drug cocktail of chemotherapy, which was linked with two deaths from meningitis and pneumonia as well as blood complications.

If successful, Tessa’s therapies would represent a triumph from Singapore’s multibillion-dollar foray in life sciences and an endorsement of a government-backed programme to entice some of the world’s leading scientists.

Connolly was working as an assistant investigator at the Baylor Institute for Immunology Research in Texas, US, when he was lured to Singapore by the state-run Agency for Science, Technology and Research in 2010.

It was inside a Zaha Hadid-designed building commissioned to encourage scientific collaboration that he met Toh, who had been mentored by Malcolm Brenner, a scientific co-founder of Tessa and the founding director of the Center for Cell and Gene Therapy at Baylor College of Medicine.

"One of the main differences here in Singapore is that they build the infrastructure and connect that with industry and talent from all around the world," said Connolly. "That we went from a meeting between two enthusiastic scientists to running such a big clinical trial speaks to the strength of Singapore’s investment into the sector."

Bloomberg

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