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Healthcare

21 October 2014

Cancer spawns multiple battlegrounds

How are university spin-outs shaping the battle against cancer?

Author: Gregg Bayes-Brown and Thierry Heles

One of the great misconceptions about cancer is that a single silver bullet will rid the world of it. If only things were that simple. The reality is that the struggle against cancer cannot be won with a one-shot solution – it is a war, with each form of cancer a potential battleground, and every new patient a fresh skirmish.

In 2012, the latest available numbers released by the charity Cancer Research UK, worldwide there were 14.1 million new cancer patients and 8.2 million deaths caused by various forms of the disease. The American Cancer Society estimates that in the US alone there will be more than 1.6 million new cases and 585,720 deaths annually.

From the constant stream of research conducted into the causes of cancer, through concepts of how to tackle cancer early, and into technology licences and oncology spin-outs created to combat the disease, the world’s universities and research institutes are very much on the front line of the fight.

The most prominent and promising of recent discoveries in fighting cancer lie in the field of immunotherapies. The areais causing much excitement with both academics and investors alike, and is causing a veritable gold rush as investors look to back potential winners. According to David Mott, partner at New Enterprise Associates, the field could be worth $35bn in the next 10 years.

It is also a field entirely driven by research conducted by top universities and institutes and the ensuing spin-outs. Three such firms causing a real stir in the field are Juno Therapeutics, Adaptimmune and Kite Pharma.

Regular readers of Global University Venturing have probably become well acquainted with Juno Therapeutics. Since launching in December of last year and subsequently tagged as a spin-out to watch in 2014 by Global University Venturing, the US-based joint venture involving Fred Hutchinson Cancer Research Centre, the Seattle Children’s Research Institute and Memorial Sloan-Kettering Cancer Centre has made numerous headlines, both in Global University Venturing and at other news sites, for two reasons.

First is the astonishing amount of money it has raised. Shortly after launch, the company secured $120m in series A backing, which quickly rose to $176m by April. Not content there, the company held a series B round worth $134m – not too bad for a company less than a year old. Backers include Rockefeller family venture capital firm Venrock, Amazon CEO Jeff Bezos’s personal investment vehicle Bezos Expeditions, oil money investment vehicle Alaska Permanent Fund, and University of Chicago’s tech transfer unit turned spun-out venture capitalist firm Arch Venture Partners.

Second, and more important, is the technology that has been attracting the tidal wave of investment. Known as chimeric antigen receptors, or Cars, Juno’s intellectual property (IP) is capable of reprogramming the body’s T-cells to target cancer. In essence, it turns the body’s immune system, normally a casual bystander when the body is being ravaged by cancer as it cannot differentiate between cancer and healthy tissue, into the highly-evolved weapon against disease it is supposed to be. Following Cars therapy, the reprogrammed T-cells identify and target cancer, delivering a precise immunological payload to tumours – the oncology equivalent of a missile strike.

What is more, the technology can be modified to work on a range of tumours, allowing it to be deployed against a number of different cancers. In addition, the therapy works as a standalone, with further development of cars potentially eliminating the need for risky and damaging treatments such as surgery and chemotherapy.

The technology is not limited to Juno. In fact, the company became embroiled in a legal battle at the start of its life with University of Pennsylvania and pharmaceutical giant Novartis, which signed a $20m development deal with the university in 2012, over copyright infringement which is still continuing.

However, both sides have shown major successes with their initial trials. In phase I and II trials at Juno, 88% of patients saw a complete remission in their cancers, while Novartis’ first patients are still cancer free four years later. And while that might be reason to celebrate, the trials have come at a cost. Two patients have died during Juno trials due to the modified T-cells multiplying out of control and attacking healthy tissue, while the Pennsylvania trials may nearlyhave led to the death of a six-year-old child for the same reason.

Cars are not the only approach an immunotherapy firm can take. In fact, half of Juno’s approach centres on T-cell receptors (TCRs). For UK-based Adaptimmune, TCRs are 100% of its focus. Spun-out from Oxford Uni-versity in 2008, the company’s therapies not only work on cancer, but could also be applied to infectious diseases. While closely related to Cars, Adaptimmune attests that TCRs are more versatile, allowing the company to target a wider range of cancers. Similar to Cars, TCR therapy works by extracting blood from a cancer patient, and then using a technology originally developed to fight HIV to alter T-cells in the blood genetically before reinfusing them into the patient

Currently, Adaptimmune is running trials in the US targeting melanoma, sarcoma and ovarian cancer in the US, and is planning to start EU trials in the near future. One such trial is due to begin in 2015, and will look closely at applying TCR-therapy to breast cancer. The funding for the trial came from the UK’s Biomedical Catalyst Fund, which provided £2.1m ($3.5m) out of its £180m pot.

Earlier in the year, the company signed a collaboration and licensing agreement with pharmaceutical conglomerate GlaxoSmithKline which could be worth up to $350m over the next seven years for the firm, with additional money on the table should the firm hit commercialisation targets.

In addition, Adaptimmune raised $104m in an oversubscribed series A last month. Led by New Enterprise Associates, Oxford University, OrbiMed Advisors, Wellington Management Company, Fidelity Biosciences, Foresite Capital Management, Ridgeback Capital Management, Novo A/S, QVT, Rock Springs Capital, Venbio Select and Merlin Nexus, and unnamed previous investors also participated.

University of California Los Angeles spin-out Kite Pharma has also found the financial winds behind it. Raising $35m last year, for which the firm was awarded Global University Venturing’s 2013 Investment of the Year, the company went on to both raise a further $50m this year ahead of an initial public offering (IPO), which brought in $128m – $13m more than the company had targeted.

The company, launched in 2009, is utilising both Cars and TCRs in a platform it is calling engineered autologous cell therapy. Despite differentiating its technology with the trademark Eact, the approach is broadly the same to both Juno and Adaptimmune.

Along with the positive IPO result, Kite had more good news over the summer from its trials. Of 13 patients treated for aggressive non-Hodgkin lymphoma, eight were in complete remission while four showed partial remission. Kite is also planning to file an investigational new drug application before the end of the year to conduct a trial with the drug KTE-C19, which will also target non-Hodgkin lymphoma.

While immunotherapies are potentially opening the door to treating a large number of cancers, the situation could also be dramatically improved with more efficient diagnostic technology to catch the disease early enough for the prognosis to still be good. As with immunotherapy, there are several university spin-outs working hard on various technologies that can catch cancer before it becomes critical.

Oxford University spun out Enhanced Medical last month, commercialising research called Oxford electromagnetiacoustic (OxEma). The technology uses, as the name suggests, a combination of electromagnetic and acoustic waves to detect cancerous tissue. OxEma produces clinical data similar to that of an MRI scanner, but its functioning is similar to an ultrasound device, making it faster, cheaper and more usable in remote areas far from the nearest hospital.

Oxford’s Isis Innovation has entered a partnership with Canada-based Centre for Imaging Technology Commercialisation to accelerate the product’s market entry. For now, Enhanced Medical’s aim is to focus on early-stage prostate and liver cancer detection.

Also focusing on prostate cancer detection is Durham University spin-out FScan. The company exclusively licensed its product to UK-based pharmaceutical and development company Glide Pharma in August this year to market the product globally. The financial terms of that deal remain undisclosed.

The product is a non-invasive test which measures levels citrate, a derivative of citric acid, in seminal fluid. Glide Pharmais working on bringing the test to market in the US first, followed by Europe. The company also acquired the rights to adapt FScan’s technology for other cancers and diseases.

When it comes to expanding cancer detection technology to other diseases, Nirmidas, a biotech spun out fromStanford University, is one step closer to achieving its goal than others.

Nirmidas, which raised a $2m seed round in August, is commercialising a signal enhancing fluorescence enhancing plasmonic gold technology, dubbed pGold, developed at Stanford some 10 years ago but only brought to market in March 2014. Like FScan’s, the technology is non-invasive. A specialised dye is able to track biomarkers of diseases such as cancer, auto-immune disorders or diabetes while the diseases are still in their early stages – it is 100 times more effective than current dye. Perhaps more uniquely, however, Nirmidas is planning, long-erm, to integrate the disease detection into wearable healthcare.

University of California Los Angeles spin-out ImginaAb is also working on diagnostic tools to detect prostate, ovarian and pancreatic cancers, and attracted $20m series B in June for further development. Its total funds now stand at $33.5m, following a 2012 series A round of $12.5m. It also has 30 collaborative agreements in place with global pharma outfits, not just concerning cancer but also immune, inflammatory and neurodegenerative diseases.

Among its investors are Mérieux Développement, investment arm of French life sciences company Biomérieux, Novartis Venture Fund, Cycad Group, Nextech Invest and Momentum Bioscience.

ImaginAb is able to engineer antibodies into smaller protein fragments that seek out their targets and light up on positron emission tomography (Pet) scans. Pet scans are 3D images of functional processes in the body, and combined with ImaginAb’s technology they are helping doctors visualise disease on a molecular level.
Its lead product is currently in a phase II clinical study.

Valérie Calenda, partner at series B lead investor Mérieux, explained the implications of ImaginAb’s technology further: “ImaginAb’s prostate cancer imaging programme has demonstrated impressive clinical data. The sensitivity and specificity of an antibody fragment approach also has the potential to change the way we understand occult disease, for example the non-metastatic, or M0, patient population in castrate-resistant prostate cancer.”

Overall, spin-outs focusing solely on early-stage cancer detection are still far and few between, and, as stated above, investments in these companies are even rarer and usually small. Two other cancer detection spin-outs that received money this past year are Yale’s IsoPlexis at $1.3m and National University of Singapore’s Endofotonics at $560,000 – almost petty cash compared with Juno Therapeutics’ staggering $310m. Whether this reality is due to the small number of companies dedicated to this area of medicine, a lack of interest by investors or a combination of both is unclear, and yet, the spin-outs demonstrate promise.

Copyright Mawsonia Limited 2010. Please don´t cut articles from www.globaluniversityventuring.com or the PDF and redistribute by email or post to the web without written permission.

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