Contract Number 214137

Biofunctionalized Metal and Magnetic Nanoparticles for Targeted Tumor Therapy

NANO3T

Sp1-cooperation Collaborative project

Small or medium-scale focused research project Start date of project: 01 August 2008

Duration: 36 months

Deliverable D6.1 Month 12

Market study

Dissemination and use plan

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Nano3T

MARKET ANALYSIS

August 2009

Interuniversity Microelectronics Centre

Author: Maria Cristina de Joncheere

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1. Introduction 2

2. Market Environment 3

2.1. Prostate cancer 5

Etiology

Treatment

2.2. Pancreatic cancer 8

Etiology

Treatment

3. Future outlook for cancer therapies : clinical trials 12

3.1. Clinical trials for prostate cancer 13

3.2. Clinical trials for pancreatic cancer 14

3.3. Clinical trials for nanoparticle-mediated cancer therapy 15

4. Market Parameters 17

4.1. Market Drivers 17

4.2. Market restraints 18

4.3 Market challenges 19

4.4 Market opportunities 22

5. Market size 23

6. Nanoparticle-Mediated energy based therapies 27

6.1. Industry impact 28

6.2. Technology evolution 31

6.3. Geographic distribution 32

7. Industry Participants 32

7.1. Energy-based cancer therapies 34

7.2. Nanoparticle-mediated energy-based cancer therapies 37

7.3. Companies marketing nanoparticle-based, 43

energy-activated drug delivery.

References 45

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1. Introduction

Cancer remains a prominent health concern afflicting modern societies, affecting an estimated

1,473,180 new cases and 562,340 deaths in 2008 alone. These staggering statistics make

cancer a leading cause of morbidity and mortality worldwide, second only to cardiovascular

diseases.

In 2008, more than half of all new cancers were of the prostate, breast, lung, and colon/rectum.

While significant progress has been made in reducing the medical burden that these individual

cancer types pose, a notable increase has been chronicled in the incidence of other cancer

types including esophageal cancer for men, pancreatic cancer for women, and liver cancer for

both men and women.

The changing demographic patterns describing cancer incidence and mortality call for a

reevaluation and prioritization of current treatment and diagnostic approaches. Current

therapeutic options for cancer rely on three principal pillars, namely surgical resection,

radiation and chemotherapy; all three with their own strengths and shortcomings. Some

prominent limitations shared by all three treatments are however the dose-limiting toxicity,

lack of specificity and morbidity associated with their application.

Recently, there has been growing interest in the development of novel therapeutic options for

the early and site-specific treatment of cancers that are able to circumvent many of the above

mentioned limitations. Nanoscale therapeutics in particular have emerged as promising

modalities for cancer treatment as they afford both the potential for targeted therapies as well

as the selective activation of therapeutic potential. Additionally, the improved and often novel

physical, chemical and biological properties that arise from reducing a material to the

nanometer scale allow optimizing specific material characteristics such as their

electromagnetic properties and their biological interactions at the molecular and cellular level.

All these factors combined have the potential of improving the therapeutic index of current

and developing cancer treatments.

Compared to alternative small molecule therapies, nanoscale therapeutics have a number of

benefits, including but not limited to: improved circulation time, higher payload capacity,

reduced toxicity to healthy tissues and improved anti-tumor efficacyi. However their

widespread adoption as standalone or complementary treatments has yet to be realized. One

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key challenge limiting their use has been the optimization and complementation of the

physical chemical and biological properties necessary to allow for specific targeting, reduced

toxicity, improved bioavailability and immune evasionii.

The bulk of current utilizations for nanoparticles are as drug carriers or novel drug delivery

agents, a field that is of great interest for the large pharmaceutical companies. A smaller but

emerging field of nanomedicine is that of nanoparticle colloid formulations as active

substances or components in targeted therapies. It is this classification of nanodrugs that are

the focus of this report, with an emphasis on their use in energy-based therapies. Owing to the

early development stage of nanotechnology-based drugs and therapies any prediction of the

market volume is very speculative, however many of the companies pioneering

nanotherapeutic methods see their target market in the range of several hundred million euro

for the first generation of their products. These numbers will add up to about one billion euro

for dendrimer and magnetic nanoparticle applicationsiii.

2. Market Environment

The burden of cancer can be expressed in three measures: incidence, mortality and prevalence.

Incidence is the number of new cases occurring in a population per year and can be expressed

as an absolute number or as a rate per 100 000 persons. Mortality is the number of deaths

occurring and can be expressed as rate per 100 000 persons per year. Prevalence describes the

number of individuals currently alive with the disease at a certain point in time.

The aggressiveness, severity and by extension prognosis and choice of appropriate treatment

for a malignant neoplasm is evaluated through a process of staging. During this process,

physicians categorize patients based on physiological, clinical and pathological characteristics

of the tumor on the basis of imaging studies, blood tests and histological classification

respectively.

According to the WHO, the number of cancer-related mortalities is projected to increase 45%

from 2007 to 2030 (from 7.9 million to 11.5 million deaths), influenced in part by an

increasing and aging global population. New cases of cancer in the same period are estimated

to jump from 11.3 million in 2007 to 15.5 million in 2030iv.

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A cross-border epidemiological study conducted by ESR shows that prostate cancer is the

most prevalent of cancers in Europe in men, accounting for almost 27% of all cancer cases in

2006 in the EU. After prostate cancer, the most frequent types of cancer worldwide (in order

of the number of global deaths) are lung cancer (18%), colon/rectum cancer (15%) and

bladder cancer (7.5%). Conversely lung cancer accounts for 31.4% of all cancer-related

deaths in Europe, followed by prostate cancer (13.5%) and colon/rectum cancer(12%).

The most frequent cancer types in women are: breast cancer (36%), colon/rectum cancer

(15%) and lung cancer (8%). Cancer-induced deaths in women follow much the same pattern

as that of incidence, with breast cancer accounting for 30%, lung cancer 15% and

colon/rectum cancer 16%. It is interesting to note that in women, but not in men, pancreatic

cancer makes a significant contribution to total cancer incidences and deaths, affecting more

than 3% of women in 2006 and accounting for almost 8% of cancer-related deaths in the same

year.

v

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Figure 1 Estimated incidence and mortality, by gender. Age standardized rate (European) per 100 000.

2. 1 Prostate cancer

Prostate cancer is a malignant tumor which arises in the prostate gland, a gland in the male

genitourinary system located just below the urinary bladdervi.

Prostate cancer contributes significantly to the worldwide cancer burden, being the most

frequent malignant neoplasm in men and the 4th most prevalent cancer worldwide, although its

incidence and societal burden differ by geographic region, and racevii. In Europe, the

estimated age adjusted incidence rates (European standard population) for prostate cancer are

10.23 per 100 000 peopleviii. Prostate cancer-caused mortality affected 346,753 men world

wide in 2008, and 109,407 persons in the EU aloneix.

Etiology

Prostate cancer typically arises from the malignant transformation of the secretory or luminal

epithelial cells, and is as such categorized as an adenocarcinoma. Although prostate cancer is

glandular in origin, the secretory cells of the gland are not themselves the culprits or site of

neoplastic transformation. Rather, it is currently hypothesized that neoplastic lesions of the

prostate are typically derived from basal precursor (stem) cells of secretory differentiation that

are the chief origin of malignant mutation. Although not yet fully characterized, factors

precipitating malignant transformations of the basal precursor cells include increasing age,

genetic predisposition, environmental factors and diet. Consistently, approximately 70% of

the male population above 80 years of age develops prostatic neoplasia.

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Staging prostate cancer

The process of staging the severity of prostate cancer is valuable as a guide for treatment

choice and for determining patient prognosis. The four stages of prostate cancer are described

in the figure below:

As mentioned above, cancer staging is based on imaging data, laboratory tests and histological

pathogenesis. These factors are applied in prostate cancer as follows:

Imaging

Trans-rectal ultrasound imaging is used for biopsy needle guidance, delineating and measuring

the size of focal lesions. x

Serum PSA

Blood tests used typically screen for the prostate-specific antigen (PSA); the concentration of

which has been found to be strongly correlated with age and is present in most cancer patients

at concentrations equal to, or higher than, 4ng/ml.

Histological pathogenesis

The pathological classification of an adenocarcinoma of the prostate is typically based on the

Gleason score. This grading system is based on changes glandular architecture and the

increased invasion of malignant cells into pancreatic stroma. According to this model, the

development of adenocarcinoma of the prostate occurs in five pathological stages ranging

from retained normal acinar and ductal architecture (score 1) to almost complete loss of

cellular polarity, sporadic luminal differentiation as well as stromal invasion (score 5)

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xi

Current treatments

Currently, men suffering from prostate cancer can choose from five different courses of

treatment namely: watchful waiting, external beam radiation therapy, radical prostatectomy,

brachytherapy, intensity-modulation radiation therapy (IMRT) and partial prostate ablation.

The choice of one or a combination of these treatments is made depending on the

aggressiveness, the staging assessment and the persons’ overall health. An overview of

treatment cost, in the USA, over a two year period as well as the relative distribution of

treatment of choice per stage of the disease is provided below. What can be seen from this

overview is that even the simplest treatment modality, namely watchful waiting, incurs

average costs of $1,218 dollar a year on medical visits. It is further of note that existing

minimally invasive targeted therapies, such as the implantation of radioactive seeds

(Brachytherapy) and IMRT are by far the most expensive treatment modalities, costing an

estimated $14,436 and $25,536 per year respectively.

As can be seen in the table entitled “treatment distribution: prostate cancer” cancerous lesions

diagnosed in either stage I or II are preferentially treated with surgery, whereas later stage

lesions are treated primarily with chemotherapy. When applied correctly, the energy-based

treatments used to treat prostate cancer (including EBRT, partial prostate ablation,

brachytherapy and IMRT) have effectiveness rates ranging from 56% for EBRT to 78% for

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brachytherapy and IMRT and 82% for partial prostate ablation. Recovery rates are equally

variable, with patients typically requiring one week or less for complete post-treatment

recovery for brachytherapy and partial ablation or suffering from chronic fatigue for 1-2

months after receiving EBR treatment.

Invariably, however, the greatest hurdle facing prostate cancer treatments is that of side-

effects; notably urinary incontinence, obstruction or infection as well as impotence.

xii xiii

Figure 2: Average cost and treatment distribution for the main therapeutic modalities used to treat

prostate cancer

2.2 Pancreatic cancer

According to the IARC, pancreas cancer is the 13th most common cancer worldwide, with

over 232 000 new cases occurring each yearxiv. In Europe, the estimated age adjusted

incidence rates (European standard population) varied between 10.96 per 100 000 in men to

7.87 per 100 000xv in women, with an estimated total mortality of 97 000 people in Europe

alone in 2008xvi (or 11.64 per 100 000 in men and 7.98 per 100 000 in women). The apparent

equivalence between incidence and mortality rates of pancreatic cancer is in great part

explained by its aggressiveness and its typically delayed diagnosis.

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Cancer of the pancreas is one of the most aggressive human tumors with a five-year survival

rate of less than 5% and as many as 90% of diagnosed patients have metastatic or local

spreading of the tumor. Survival and prognosis vary depending on the initial site of malignant

transformation within the pancreas, whether in the head, body or tail. 80% of tumors

occurring in the body or tail are stage IV lesions at time of diagnosis, whereas 33% of those in

the tail are equally advanced at diagnosisxvii.

Etiology

Neoplasms of the pancreas can be broadly divided into neoplasms with predominantly

exocrine differentiation and neoplasms with predominantly endocrine differentiations.

Between 90 and 95% of pancreatic cancers are moderate to well-differentiated

adenocarcinomas derived from the pancreatic ductal epithelium (exocrine neoplasms), with

infiltrating ductal adenocarcinoma being the most prevalent of these. Conversely about 5% of

pancreatic cancers originate from the pancreatic islet cells (endocrine neoplasms). Other rare

types of pancreatic cancer include sarcomas, lymphomas and cystenoadenomasxviii

Advancing age is one of the strongest predictors for the development of pancreatic cancer,

with majority of cases occurring at the age of 65 or above. Environmental and dietary factors

are also thought to be involved in its pathogenesis, in particular tobacco smoking accounts for

an estimated 29% of pancreatic cancer cases. Excessive red-meat consumption and heavy

alcohol consumption are also thought to be involved. Finally chronic diabetes and pancreatitis

are associated with a 2-fold and 10-fold increased risk respectively.

Staging

The staging of pancreatic cancer is based on imaging data, laboratory tests and histological

pathogenesis. These factors are applied as follows:

Histological pathogenesis

Most ductal adenocarcinomas are moderately to well differentiated, with well-developed

glandular structures; they are however, unlike normal tissue embedded in fibrous stroma.

Differentiation between poorly differentiated, to well differentiated and normal tissue is based

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on the mitotic activity of cells, appearance of cell nuclei and cytoplasm, cellular polarity,

nature of stroma and mucin production.

Histopathology

There is currently no unequivocal histochemical or immunohistochemical marker able to

unequivocally distinguish pancreatic from extra-pancreatic adenocarcinoma, some markers are

used to separate ductal from non-duct type adenocarcinoma, and these are:

Mucin (MUC1, MUC3 and MUC 5/6)

Carcinoembryogenic antigen (CEA)

Cytokeratins and vimentin: keratin patterns of non-duct type, gut carcinomas, and

ductal carcinomas are different, thereby making it possible to differentiate between

these types based on their CK profiles (duct carcinomas for example lack CK20, a

cytokeratin typically present in normal tissues) and are typically negative for vimentin.

Imaging

Currently the most important tests for establishing the diagnosis of pancreatic carcinoma are

ultrasonography, and computerized tomography or magnetic and resonance imaging,

endoscopic retrograde cholangiography.

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Current Treatments

Standard cancer therapies for pancreatic cancer vary according to the stage, malignancy and

time of diagnosis.

Table 1: overview of treatment recommendations by stage of tumor at time of diagnosis

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Source: National cancer institute. xix

According to a study conducted by Wilson and Lightwood, the mean duration of treatment for

pancreatic cancer was 12.6 months. During the period of treatment, mean monthly anti-cancer

treatment and additional pharmacotherapy costs were $3,771 and $3,196 respectively. In the

last twelve months of life, months -3, -5, and -2 (death = 0) were most expensive with average

spending of $65,557, $58,820, $47,727 respectively. Breakdown of costs in the three most

expensive months was: anti-cancer agents (82%), hospitalization (15%), additional

pharmacotherapy (3.0%), and clinic visits (0.5%)xx.

Figure 3: Estimated costs associated with pancreatic cancer treatment, with 84% of direct medical costs

relating to hospitalization costs. (A) Breakdown of direct medical costs associated with hospital costs,

outpatient costs and long-term care costs. (B) Breakdown of hospital costs associated with room/board,

medications, laboratory, surgery, radiology and misc. (Data from Wilson and Lightwood)

3. Future outlook for cancer therapy: Clinical trials

The division of resources devoted to innovation and development in the field of cancer

treatments to a large extent resembles the global incidence and morbidity of the disease. As is

shown in the figure below, larger proportions of clinical trials are allocated the most

prominent forms of cancer (see figure 1). Thus clinical trials focusing on lung cancer,

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colorectal cancer, breast cancer and prostate cancer, the most common forms of cancer,

account for 15%, 14%, 14% and 6% respectively, almost 50% of all clinical trials.

xxi

Figure 4 2003-2008 Percentage of oncology trials per indication

3.1 Clinical trials for prostate cancer

An analysis of ongoing clinical trials reveals that 54% of those clinical trials identified for the

purpose of this market study were treatment-focused, whereas 13% and 11% were dedicated to

the validation of laboratory tests as well as screening/prevention methods respectively. The

former observation resonates with ongoing initiatives emphasizing the importance of early

diagnosis and screening for the detection of malignant lesions and can be considered largely

complementary to the treatment modalities in question.

Of the treatments under development, as can be seen in the right hand panel of the figure

below, there was a relatively equal distribution between treatments for prostate cancer in

stages 1 to 4 as well as recurrent cancers. It is striking however that only 3 clinical trials out

of those identified (total 214) were aimed at treating hormone resistant cancers.

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54%

11%

9%

13%

2%

11%

treatment

screening/prevention

diagnostic

laboratory

support

other

0%15%

21%

19%

23%

22%

Hormone resistant,

Stage I

Stage II

Stage III

Stage IV

Recurrent cancer

Figure 5: Analysis of ongoing clinical trials for prostate cancer. On left: distribution of clinical trials by

aim of trial. On right: distribution of clinical trials by targeted stage (prostate cancer).

Most clinical trials aiming to test the effectiveness of prostate cancer treatments were in phase

II, while only 2% of the trials identified were in phase IV or later. It is further of note that

most treatments were combination or adjuvant treatments, approximately 100 were focused on

novel forms of administration or delivery for existing medications. 2 clinical trials used

nanoparticles as novel delivery systems.

11%

16%

11%

40%

2%

18%2%

preclinical

phase I

Phase I,II

Phase II

Phase II,III

Phase III

Phase IV

Figure 6: Distribution of ongoing clinical trials by current phase (prostate cancer)

3.2. Clinical trials for pancreatic cancer

Approximately 377 clinical trials addressing the screening diagnosis or treatment of pancreatic

cancer were identified. Of these 224, or 60% study treatment options for pancreatic cancer,

14% aimed at the improvement of laboratory tests and 8% for support.

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60%

1%

5%

14%

8%

12%

treatment

screening/prevention

diagnostic

laboratory

support

other

Figure 7: Analysis of ongoing clinical trials for pancreatic cancer: distribution of clinical trials by aim of

trial.

Approximately 81% of all treatment-based clinical trials identified were either in or between

phase I and phase II. 10% were in a preclinical phase and only 1% was in phase IV. As with

the clinical trials for prostate cancer treatments, most treatments concerned combination or

adjuvant treatments and novel delivery or administration forms.

Only 3 clinical trials were identified in which nanoparticles were used for the administration

of drugs. No clinical trials focusing on clinical trials as novel treatment agents, in and of

themselves, were identified.

10%

24%

17%

40%

2%6% 1%

preclinical

phase I

Phase I,II

Phase II

Phase II,III

Phase III

Phase IV

Figure 8: Distribution of ongoing clinical trials by current phase (pancreatic cancer)

3.3. Clinical trials for nanoparticle-mediated cancer therapy

A list is given below of ongoing or recent clinical trials, identified by IMEC, in which

nanoparticles are used for treating cancer. Notably, liposomal, and colloidal emulsions are the

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most mature and common in the field and are invariably classified as drug-delivery agents as

opposed to therapeutic agents in and of themselves. This feature may explain to a great deal

their wider adoption. Novel drug delivery forms for existing medications allow for extension

of patent life time and the re-introduction of compounds formerly deemed unsuitable due to

e.g. insolubility. Indeed pharmaceutical companies are most active in the field. Nanoparticles

as therapeutic agents or as carriers for biotherapeutics are however starting to appear

(Nanospectra, Magforce…).

Table 2 Overview of ongoing and completed nanoparticulate clinical trials for cancer treatment.

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4. Market Parameters

In this section a closer look will be given into the key challenges faced by all players of the

cancer therapy market, as well as the drivers and restraints governing industry development.

(Source: Frost & Sullivan, 2008)

4.1. Market Drivers

Increased patient awareness

One of the major reasons for growth in his market has been the activity of organizations and

research institutes that promote cancer awareness amongst the public and health professionals.

A positive impact on the market is witnessed as patients are receiving additional treatment

options.

Demand for non-invasive therapies

Healthcare expenditures are to rise as a result of an aging population with the concomitant

increased burden of risk factors for- and incidence of- chronic diseases including cancer.

These factors result in the increased need and demand for health monitoring, treatments,

medication etc. The resulting strain on the socioeconomic healthcare is a strong driver for

non-invasive therapies which reduce recovery periods and thus the use of hospital or

healthcare centre resources.

Necessity for non-invasive therapies

An increasing demand for minimally invasive and non invasive alternatives to existing

treatments such as chemotherapy and surgery for cancer is driving the growth of radiation

therapy in particular. Growing patient awareness about treatment options, requirement for

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treatments with fewer complications and side effects and shorter hospitals stays and recovery

periods are preferred over radical procedures such as major surgery, wherever feasible.

Necessity for early intervention

Several cancer types are associated with very high mortality rates. A very high level of

improvement is needed to improve the prognosis and treatment of such major cancer

indications. With the increasing patient population, the implementation of technological

advancements in cancer treatment and diagnosis is likely to improve the cancer treatment

profile. Such technological advancements and innovative approaches will also enable the

prognosis of cancer indications. This is perceived as being an important factor driving the

cancer therapy market.

Rise in incidence with increasing population

The increase in the number of incidences of all major cancer indications, coupled with the

increase in the aging population is a major driver for market growth. With the aging

population profile, approximately 40 to 50% increase in the incidences is expected for major

types of cancer such as prostate cancer, breast cancer and lung cancer. This factor is expected

to be a high-impact factor for the coming 7 years.

4.2. Market Restraints

Lack of efficacy of products

Cancer remains a significant area of unmet clinical need. It is the second most important

cause of death in Europe after cardiovascular diseases. It is anticipated to overtake

cardiovascular disease by the year 2012. Cancer therapeutics currently aim at the treatment of

symptoms in order to prolong the life of the patient rather than offering a total cure. The

complex, multi-factorial nature of cancer indications makes the discovery of a complete cure

unlikely and this factor is anticipated to have a significant effect.

Patient stigma tampers uptake of treatment

A majority of the patients are not comfortable discussing embarrassing medical issues, and

research shows that cancer is still considered taboo. Many men avoid visiting the doctor for

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fear of physical examination necessary for the diagnosis of prostate cancer. They are also

afraid of the complications such as incontinence and impotence, associated with therapy.

These factors result in men seeking medical attention when the prostate cancer has progressed

to an advanced stage, with palliative treatment being the only option. This limits the patient

number and thereby restricts potential revenues within the market.

4.3 Industry Challenges

Cost and time consuming regulatory compliance

The process of establishing safety, efficacy and quality of treatment prior to authorization of

commercialization is regulated through central government agencies in a complex and time-

consuming process. Government agencies may additionally be responsible for the negotiation

of price and reimbursement approval when required, but this adds additional delay to the

approval process. This parameter is, and is predicted to remain, a factor of high impact for

the industry.

Two related and to a large extent contributing considerations in the cancer therapeutics

industry are those of cost of treatment and reimbursement costs. As cost of treatment

increases, practitioners, patients and health insurers are less likely to prescribe/refund

expensive treatments with only moderate benefits compared to alternative treatments.

Cost of development

A new drug is estimated to cost an average of $124.0 million and takes an average of 12.5

years to pass through clinical trials. These costs are attributed to the requirement of the larger

patient population and also to more complex testing procedures, particularly toxicity testing.

With oncology trials, it is more likely that only one or two patients are identified at each trial

facility and therefore staffing requirements are high while carrying out the trial relative to the

number of trial participants. Patients are often reluctant to reject unconventional treatments

when inflicted with a potentially life threatening disease, making patient recruitment difficult.

New therapeutics (such as biopharmaceuticals) are expected to be expensive due to more

stringent regulatory requirements and high cost of development. Therefore, these costs are

likely to deter new market entrants with research & development budgetsxxii.

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Lack of uniform treatment plan

Numerous molecular pathological and clinical factors affect the treatment decisions and

course. Due to the sheer volume of factors to be considered and the number of treatment

modalities available there is as yet no standardized treatment plan nor a comprehensive

comparison of the relative efficacy of each treatment per scenario.

Cost containment limits R&D spending

Due to an aging population and rising incidence of cancer, healthcare expenditure is

continuously on the increase. As a result, governments across the major global markets have

begun to prioritize their cost-containment policies in order to drive down costs. Various

methods employed by governments in their respective countries are reference pricing, delays

in approval, strict procedures, restriction on dispensing and prescribing and reimbursement

system. However, price controls on new drugs and treatment modalities reduce the margins for

manufacturers, leaving fewer revenues for future research and development (R&D)xxiii.

Patient life-time

Current trends suggest that patients are becoming increasingly aware of the treatment regimes

that exist in the market through cancer awareness campaigns and the use of the internet. There

is an increase in the sharing of information amongst oncologists and patients: their side effects

and the quality of life of the patient. Awareness challenges the critical use of products as

patients may choose to abstain from treatment if quality of life is severely deteriorated and

prolonged survival is minimal. Therefore, the future market offers an opportunity to products

that are highly efficacious and prolong survival even at a premium price. Such a trend is

likely to challenge companies to engage in research and product developmentxxiv. This factor

is however expected to have a small impact on the total decision making process in the coming

10 years.

Side-effects associated with treatment modalities

Treatment-associated side-effects are prominent challenges for the world cancer therapeutics

market. Side-effects are particularly prominent in the chemotherapeutics markets, where some

patients may experience moderate to severe reactions to the treatment. Managing side-effects

is however a concern for all treatment modalities and there is still a need to improve the

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efficacy and specificity of cytotoxic treatments in order to eliminate these side-effects.

However, this challenge is yet to be overcome and is likely to have a significant influence

throughout of the forecast period.

A recent report drafter by Ernst and Young, entitled “Nanotechnology in medicine: new

perspectives for the life sciences industry” further ranked the importance of the

aforementioned challenges according to how important they are expected to be for the

development of the nanomedicine industry in the coming years (see figure 9 below). As can

be seen from the diagram bellow managing and forging scientific and technological innovation

(through the protection of IP, attracting scientific talent and find appropriate alliances) is

deemed critical at this time. Considerations proper to more mature technologies, such as

regulatory compliance, clinical trial management and pricing pressures are deemed less

pertinent to nanotechnology development.

Figure 9: Significant challenges for the commercialization of nanomedicine at present and in the future

xxv

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4.4 Market opportunities

Just as above the main challenges, weaknesses and threats facing the industry were stipulated

in this section the opportunities within the market will be described (according to Frost &

Sullivan, 2008).

Growth of, and within, the industry are likely achieved by fortifying and expanding the

research and development activities, particularly those that are directed towards large (or

growing) target populations. Investment in R&D for new devices that focus on immediacy

and a predictable long-standing future will result in favorable market growth. Since the

medical technology market is one largely driven by innovation, a strong R&D base allows for

market growth through the introduction of new products and scientifically proven

technologies.

Given the current economic situation, growing ones market share is particularly important to

secure the funds and assets necessary to keep float. Increasing market share can be achieved

by prioritizing quality of the product and of the service. Firstly, a good initiative is therefore

to bring about positive awareness among the patient population about minimally invasive

procedure and the technology belying it. Secondly, as cancer treatments are usually long-

term, good will between the manufacturers and patients will help increase market share of

companies. Earning goodwill is dependant on excellence in the service provided.

Manufacturers need to increasingly emphasize on quality checks in order to attain brand

loyalty, which in turn would translate to increased market revenues. Lastly, partnering with

specialists and referring to practitioners would help in scouting short and mid-term market

share. Investing in future clinicians, by providing regular updates and continuing education in

the field and thereby familiarizing themselves with the future clinicians would be a viable

option for growth for market participants.

In short, improving and not compromising the quality of products would surely help industry

participants tide over the pricing pressure on their products. Manufacturers should emphasize

on improvising quality by developing a product with higher predictability even in the worst or

ill-fated cases.

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5. Market Sizexxvi

The nanomedicine market as a whole is still in its early stages of development; accurate

predictions of market size are thus inevitably speculative. In a comprehensive analysis of the

nanomedicine sector, 200 companies with nanomedicine activities were identified. Consistent

with the relative novelty of the field, most of the companies active in the sector are start-up or

SMEs. Amongst 200 companies identified were 92 start-ups, 67 SMEs and 41 large

pharmaceutical or medical device companies. The nanoparticle mediated or enhanced drug

delivery accounted for an estimated $4.2 Billion in 2004 (80% of total market revenues).

Nanoparticle-based drugs and therapies have not yet been approved for marketing, this

generating no revenue as of yet. By 2015, it is expected that the total nanomedicine market

will be worth EUR 15 billionxxvii

The technology developed through this consortium is expected to find its niche within the

energy-based therapeutics market. Market information given in this section is from a recent

market report by Medmarket diligence, “Ablation technologies worldwide market: 2008-2017:

Products, technologies, markets companies and opportunities”

Energy based therapies encompass a broad range of technologies used to achieve the complete

or partial eradication or isolation of pathological or aberrant tissues to curative ends. Current

technologies used to this end, and used for the calculation of total market size are technologies

such as radiofrequency, microwave, laser/light, microwave, cryotherapy, hydromechanical,

ultrasound and thermal therapies.

Figure 10 woldwide energy therapies market vs. medical device market, 2007-2017

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Total worldwide revenues for energy-based devices amounted to $25.4 billion in 2008,

thereby accounting for almost 14% of the total medical device market in the same year.

However, like the medical device market which is growing at a compound annual growth rate

(CAGR) of around 11.7% (from 2004-2011, USA), the ablation market is projected to grow at

an average CAGR of around 11%, thereby out pacing other technologies in the medical device

market (see figure 7). Interestingly however the growth rate within countries of the European

Union varies significantly from this average growth rate, with the Benelux predicted to

experience a CAGR of 22.2% between 2008-2017; France is predicted to experience 16.5%

growth in the same time frame and Germany 14.7%.

Akin to the medical device market, the Americas hold majority market share, accounting for

57% of total revenue in the industry. Europe as the second most prominent geographic entity

accounts for 22% of the total market revenues, closely followed by Asia pacific holding 17%

market share.

Figure 11 Woldwide ablation market by country/region, 2008

Apart from geographic distribution, market revenues are also energy-modality/technology

dependent. As shown in figure 12 technologies using electrical energy for tissue ablation

generate a vast majority of the total revenues in the industry, accounting for 42% of the

revenues. Radiation on the other hand accounts for almost a quarter of market revenues,

whereas light, radiofrequency and ultrasound-based technologies together generate another

26% of total market revenues.

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Figure 12 Woldwide market by technology, 2008

By extension, projected growth rates between 2003 and 2013 is also technology or modality

dependent, interestingly the above mentioned proportions per modality do not apply to their

projected growth rates. Microwave, radiofrequency, cryogenic, thermal and ultrasonic –based

technologies are expected to experience most dramatic growth (>15% CAGR) in the coming

years. Whereas electrical, hydromechanical, light and radiation based ablation is expected to

continue growing, albeit at a slower rate (<12% CAGR).

Figure 12: Projected market growth for energy-based ablation technologies. On left: predicted CAGR per

energy modality. On right: projected market revenues per energy modality between 2007-2017

The buoyancy in the energy-based sector is due partly to increased uptake of these

technologies and partly due to introduction of technology refinements, which in turn lead to

increased usage. There is also the demographic factor; many of the conditions for which

ablation products are used are commoner among older than younger patients, and lengthening

life expectancy makes its own contribution to market growth.

27

The clinical application of the ablation technologies is most prevalent in cardiovascular

applications; accounting for 63% of the total market. However the second and increasingly

prominent use is for oncological treatments, which currently occupy 28% of revenues.

Figure 13: Overview of energy-based ablation therapies market by clinical application (left) and by cancer

type (right).

Below see the current distribution of ablation therapy markets across different solid tumor

types. As can be seen in this figure, the use of ablation technologies for gastrointestinal and

liver treatments was the most profitable application, generating 32% of revenues in this

market, or $2772 million in 2008. Treatment of prostate cancers with ablation technologies

generated $112 million in the same year.

Nanomedicine is referred to as the application of nanotechnology to health and life sciences.

By exploiting the improved and often novel physical, chemical and biological properties of

materials at the nanometric scale, nanomedicine promises to deliver targeted therapies with

reduced side-effects, novel imaging technologies and early diagnostics for diseasesxxviii. It is

therefore a very promising technology which lends itself to bypassing the existing weaknesses

and drawbacks of currently used oncology treatments. Indeed, over the past decade, research

into this field has been growing exponentially. In 2006, Lux research estimated that a total of

$12.4 billion were spent by local governments, corporation and venture capitalists on

nanotechnology R&Dxxix. This raising awareness and investment is apparently paying off. In

2006 global sales of nano-enabled products exceeded $50 billion, and by 2014 Lux estimates

that $2.6 trillion in manufactured goods will incorporate nanotechnology (15% of total global

output)xxx. The medical industry is contributing significantly to this global revenue;

nanotechnology-enhanced medical products that were placed on the market generated total

28

sales of approximately EUR 5.4 billion and by 2012 this number is expected to increase to

EUR 15 billionxxxi.

6. Nanoparticle-mediated targeted thermotherapy

The potential of heat as a weapon against cancer has long been recognized. Raising the

temperature of tumors not only damages malignant cells to stop disease spread, it also

weakens cancers' defenses to chemo- and radiotherapy, making such treatments more effective

at lower, less toxic doses. As yet, however, heat therapy has failed to make the transition into

routine clinical practice, owing to the practical difficulties of delivering heat safely and

efficiently to the target tumor.

The main aim of thermal ablation is to destroy an entire tumor by using heat to kill the

malignant cells in a minimally-invasive fashion without damaging adjacent vital structures.

Heat from various sources can be used with equal effectiveness to destroy tumor cells. As

long as adequate heat is generated throughout the tumor volume it is possible to eradicate the

tumor. A major advantage of thermal ablation is the ability to treat a tumor with a defined

volume in sites where surgery itself is impossible or where organ preservation is needed or

desired.

Currently, thermal ablation is performed by an interventional radiologist and is much less

invasive than open surgery. Thermal ablation can be an alternative or complement to current

cancer therapies such as surgery, radiation therapy and systemic chemotherapy. There is a

marked increase in the use of targeted energy-based therapies, whose aim it is to reduce

systemic damage to normal or benign cell types and thereby reducing side-effects or

complications associated with current therapies.

The use of nanoparticles for targeted thermal therapy can be broadly categorized as shown

below in box 1.

29

Note: the exclusive use of nanoparticles as imaging agents has in this case been excluded unless explicitly

mentioned that they serve a dual purpose of treatment and diagnosis/imaging.

6.1 Industry Impact

The impact of an institute, university or company on the overall field will be evaluated, for the

purpose of this report, by means of the number of patents filed and frequency of citation.

The bar chart below illustrates the number of patents filed per university or company. As seen

in figure 12, The University of Rice, is by far the main patent assignee, followed by Sirtex

medical, Nanobiotix, the University of California and Magforce. The university of Keele,

MIT, Intematix corp. Triton Biosystems, and Abbott (amongst others) hold an intermediate

30

number of patents, typically 3. Finally the majority of companies and institutes active in this

field hold one-two patents, some examples are given below.

2

2

2

2

2

2

2

2

2

3

3

3

3

3

3

3

3

3

4

6

6

10

14

therm med llc

American Biosciences

cytogen corp

nanoprobes

Midatech ltd

Boeing

Philips

Schering AG

Fujif ilm

Univ. New York

Toto Ltd

Abbott

Univ. Texas

Triton Biosystems

Intematix Corp

MIT

Univ. Keele

health research inc

Magforce

Univ. California

Nanobiotix

Sirtex medical

Univ. Rice

Figure 14 major assignees with maximum relevant patent families

Similar categories and patterns as those described above can be applied to describe the most

cited patent assignees. Majority citation is held by the University of Rice and Sirtex medical

as well as research corporation technology an individual “Gordon Robert Thomas” who was at

the time working for Schering AG (now Bayer Ag). Although patents held by this individual

appear to be both pioneering and highly influential in the field, the most recent patent was

filed in 1989 and renovation payments were not made. Intermediate cited patent assignees

include Intematix corp. Nanobiotix, Magforce, Cytogenic and Nanoprobes as well as the

University of California, New York and Northwestern.

It is of note that the industry participants are generally SMEs and start-ups, with only sporadic

participation of larger players such as Philips, Boston Scientific and Abbott.

31

1

2

2

2

2

2

2

2

3

3

3

3

4

4

5

6

6

7

7

11

16

16

25

Health research inc.

Boston Scientific

Psimei pharma plc

Ball semicon

silica gel Gmbh

magforce

Therm. Med.

Cytogenic

europ I of science AB

Nanoprobes

Northwestern

Intematic

Nanobiotix

Toto Ltd

Univ Of California

univ. New york

int. neue mat gemeinschaft

Triton Biosciences

Schering AG

research corp. tech

Sirtex/Paragon

Gordon thomas

Univ Rice

Figure 15 Most cited patent assignees

The above summarized trends can be in part explained by the age of the technology.

Illustrated below is the evolution over time of the major assignees.

Here it can be seen that the more prominent patent assignees are in most instances also among

the earlier entrants. Earlier patents filed by Sirtex/Paragon medical date back to 1996,

whereas University of Rice has patents dating back to 1999. This is in contrast to more

“recent entrants” to the field such as Abbott and the University of Keele, both of which

starting making pronounced contributions to the field around 2006 or later.

32

Figure 16 Patent publication dates by company, institute or university

6.2. Technology evolution

The chart below illustrates the total number of relevant publications per year and the priority

dates of relevant patents in the field. The trends observed below (figure 14) indicate a surge of

patenting activity post 1997, compared to previous years. An equivalent surge is observed for

publications, which seem to have increased exponentially since 2003. These trends suggest

growth of the industry and technology and thus increased patent protection being sought.

Most patents were filed in 2005, after which year there has been a progressive decline in

patenting activities, a similar decline is seen after 2007 in for publications (it is note worthy

however that the decline in patents after 2007 is only seen for priority year not for year of

publication).

0

10

20

30

40

50

60

70

1991 1993 1995 1997 1999 2001 2003 2005 2007 2009

publications

patents

Figure 17 Time distribution of patents and publications related to nanoparticle based hyperthermia

33

6.3. Geographic distribution

Most patents and relevant patent families identified were published in the USA, followed by

Europe, Japan, Australia and Canada.

Figure 18 Geographic distributions for country of original publication of patents and patent families in the

field of energy-activated nanoparticle-mediated cancer therapeutics

7. Industry Participants

Industry participants can be classified as either academic institutions/individuals, specialized

start-up companies, medical device/equipment manufacturers or material developers. An

analysis of the most prominent industry players reveals that the majority (45%) of participants

are academic institutes, universities or individual scientists. Specialized start-ups are the

second largest group represented amongst the industry participants, about 25% of participants

fall under this category. Material developers (such as Toto, TTc Ltd, Ferrotherm),

pharmaceutical companies, and equipment manufacturers make up 15%, 10% and 5% of most

prominent/active industry participants respectively. A schematic representation of the value

chain for target energy-based therapies is given below.

34

45%

25%

10%

15%

5%

Academic

start-up/SME

pharmaceutical

material

equipment

Figure 19: categories of most prominent/active industry participants.

As stated above the bulk of ongoing research in the field of nanoparticle-mediated heating is

in fact seated in non-profit organizations, research institutes and universities. These provide

the basic technologies and academic foundations for further development, commercialization

and adoption in the medical community. Indeed Nanospectra and Nanobiotix are both

originally university spin-offs from Rice University and the University of New York,

respectively.

Further maturation, optimization and testing of nanoparticle-mediated heating technologies are

then carried out by niche industry players, start-ups or SMEs. It is at this stage that the

original technology becomes amenable for commercial adoption and clinical trials are

conducted calling on sources of external funding. Magforce is currently the largest and best

known of the nanomedicine companies in this field. They are currently going through a

number of clinical trials, approximately half of their ongoing trials are currently phase II or

later.

As mentioned above, the market for energy-based tissue heating or ablation and its application

in the oncology market is a very promising one, having attracted the attention of some of the

largest medical device companies. Boston Scientific, Siemens and Philips healthcare are

amongst the larger medical device companies who have established stable and cooperative

partnerships with some of the companies mentioned above and/or filed patents in the field.

These medical device companies share in particular a growing interest in the healthcare

market, and are specifically focused on targeted, image guided therapeutic/diagnostic

technologies. Equipment manufacturers and medical device companies sell their products

directly to health care centers, hospitals, or universities, and as such represent the final

transition from immature technologies to commercial and therapeutic adoption.

35

Material developers are for the purposes of this report identified as those specialized in the

development, manufacture and delivery of nanoparticles of defined characteristics.

Micromod, Boeing, Metal LLC and Ferrotherm are amongst the companies identified

specializing in the development and manufacturing of specialized nanoparticles for energy-

based tissue heating. These companies can be active throughout the value chain, as raw

material suppliers or as in-sourced specialists.

7.1. Targeted energy-based therapies commercially available

Below is given an overview of existing therapies market by some of the largest equipment

manufacturers, along with company claims. Companies were selected based on deemed

interest (determined on the basis of patent filings, publications, clinical trial information…) in

the field of nanoparticle-mediated thermal ablation.

a. Radiation therapy

Radio Frequency Ablation (RFA) has become an increasingly common method for treating

liver cancer. RFA uses extremely high temperatures (80º-100º C) to ablate tumors.

36

Varian: Radiation therapy

Varian offers the latest advances treatment techniques available in radiation therapy today, as

well as imaging solutions. Treatments offered are in the fields of radiation oncology,

brachytherapy, radiosurgery and proton therapy.

1) RapidArc/Trilogy radiotherapy technology is a volumeric arc therapy that delivers a

precisely sculpted 3D dose distribution with a single 360-degree rotation in the linear

accelerator gantry. RapidArc uses a dynamic multileaf collimator (MLC), variable

dose rate, and variable gantry speed to generate IMRT-quality dose distributions in a

single optimized arc around the patient. This technology is two to eight times faster

than existing dynamic treatments and increases precision by allowing treatment of the

entire volume rather than slice by slice.

2) Dynamic targeting IGRT provides high-resolution, three-dimensional images to

pinpoint tumor sites, adjust patient positioning when necessary, and complete a

treatment. Using this technology allows clinicians to reduce the volume of tissue

irradiated, targeting only the tumor and sparing the surrounding normal tissue.

Irradiating less normal tissue reduces the toxicity of radiotherapy, improving the

patient's quality of life

3) The Clinac system allows for precise treatment and high resolution images due to

Waveguide—steers the beam with precision.

a. Gridded gun—fast beam-on, beam-off control.

b. Energy switch, with tight isocenter—delivers high dose quickly.

c. Bending magnet—enables a small, sharp beam focal spot

4) IBGT (Brachytherapy) treats cancer by placing radioactive implants directly into or

next to the area requiring treatment. This enables clinicians to deliver a high dose with

minimal impact on surrounding healthy tissues.

-The VariSource iX is designed with many advanced and unique features that

make it the gold standard for HDR brachytherapy.

-The GammaMedplus iX and the GammaMedplus 3/24 iX,

37

Siemens

Siemens offers a wide spectrum of radiation oncology solutions; from software, hardware and

workflow processes. Siemens offers three models of linear accelerators, all three emphasizing

treatment precision, image-guided therapies, reliability and ease of use.

1) Siemens ARTISTE™ offers a comprehensive portfolio of image-guided and advanced

treatment delivery tools, enabling clinicians to choose the appropriate treatment technique for

each patient. Using this product, radiation oncologists can perform the following treatment

modalities

• Conformal Radiation Therapy (CRT) • Intensity-Modulated Radiation Therapy (IMRT) • Image-Guided Radiation Therapy (IGRT) • Gated treatments • High-precision radiation therapy and radiation surgery (SRT/SRS) • Future advanced adaptive therapies, such as Dose-Guided Radiation Therapy™* as they become available

2) The ONCOR™ Impression Linear Accelerator is designed specifically for image-guided

radiation therapy (IGT) further being cost-effective, compact and flexible. It is sold with a

variety of upgrades, imaging and positioning tools.

3) The ONCOR™ Avant-Garde Linear Accelerator is designed for the latest clinical

applications, such as gated therapy and Image-Guided Radiation Therapy (IGRT) and IMRT.

4) PRIMUS™ is customizable to meet your needs and finances, and supports the widest range

of treatment techniques – including conventional radiotherapy, Stereotactic Radiation Surgery

(SRS), Intensity-Modulated Radiation Therapy (IMRT), and Image-Guided Radiation Therapy

(IGRT).

Boston Scientific

Boston Scientifics’ products are specifically designed for minimally invasive ablation

treatments. They are currently the second largest energy-based ablation company, second to

Medtronic and derive a majority of their revenues from RF-frequency based ablation for

cardiovascular applications. They do however have a range of RF-frequency ablation

treatments for destruction and removal of neoplasms.

38

The RF 3000® Radiofrequency Ablation System and RF Needle Electrode Families are

intended for the thermal coagulation necrosis of soft tissues, including partial or complete

ablation of non-resectable liver lesions.

1) RF3000 Radiofrequency Ablation System is an impedance-based feedback system.

2) LeVeen® Needle Electrodes are designed for open, laparoscopic or percutaneous

radiofrequency ablation, providing a cannula and a patented array design that is available in a

choice of diameters.

3) Soloist™ Single Needle Electrode is designed for the treatment of small, difficult-to-access

lesions.

4) Renegade® Hi-Flo Microcatheter is designed for distal access and exceptional flow. Its

.027" inner lumen is designed to provide high flow delivery of viscous embolic materials,

therapeutic agents and increased infusion pressures, further enhancing flow.

5) Fathom™ Steerable Guidewire combines a nitinol hypotube distal segment with advanced

microfabrication technology, creating a design to allow access to tortuous vasculature. Unlike

conventional guidewires, the nitinol hypotube distal segment is designed to transmit turn-for-

turn torque to enhance responsiveness and maneuverability.

7.2. Nanoparticle-based hyperthermal therapies

There are a number of companies currently commercializing or undergoing clinical trials for

the use of nanoparticle based tumor hyperthermia or ablation. An overview of their respective

technologies and commercial equipment is given below.

Not surprisingly, the main focus of most targeted energy-based therapies is that of reducing

side-effects and increasing specificity to malignant tissue while sparing normal tissues. In this

section an overview of the main patents held by some of the SMEs/startups active in this field

is given, in an attempt to analyze how they have each addressed the issue of specificity.

39

Magforce

Magforce is currently the first company and most clinically advanced of SMEs active in this

field to commercialize nanoparticle-mediated hyperthermia treatments. Magforce and its

underlying technology was largely developed through the work of Dr. Andreas Jordan, who

while studying the use of hyperthermia for cancer treatment came up with a way to confine the

administered heat to a well-delineated tumor using sugar coated magnetic nanoparticles.

Preliminary biological studies were originally funded by the Deutsche

Forschungsgemeinschaft, after which Dr. Andreas Jordan founded the MFH

Hyperthermiesysteme GmbH to develop the equipment necessary to administer the required

magnetic fields necessary for heat producing relaxation processes in the nanoparticles.

Further development and commercialization of the nanoparticulate matter was conducted

separately at the Instituut for Neues Materiele (INM) after which MagForce Applications

GmbH was founded by Dr. Jordan for the production of specific nanoparticles for the new

cancer therapy. In October 2005 MagForce incorporated was founded through the merger of

both previous companies.

The below table gives an overview of the patents held, by Andreas Jordan himself in this field

and those filed either under MFH hyperthermiasysteme, Magforce applications or Magforce

incorporated.

As can be seen from this table the company holds a protective right over the manufacture and

production of nanoparticles for use as targeted hyperthermia systems, for the targeting and

internalization of the nanoparticles in malignant or aberrant cells, as well as the conjugation of

the nanoparticles to active substances for targeted drug delivery. Additional patents describe

the generation and use of magnetic coils for the targeted heat generation of magnetizable

elements. It is worth noting that a recent patent lawsuit filed between MagForce and Sirtex

medical indicates their strong motivation to remain the key player in this field and protect their

intellectual rights.

40

Table 3 Overview of patents held by Magforce

41

Nanobiotix

Nanobiotix is a nanomedicine company that, unlike MagForce aims to improve targeting and

specificity of radiotherapy. The company is a spin-off of the State University of New York at

Buffalo (2003); the original technology was developed and optimized by founder and CEO Dr.

Laurent Levy. The table below gives an overview of patents held in this field by Dr. Laurent

Levy, UNY and Nanobiotix.

As can be seen in the table below Nanobiotix holds a number of patents specifically relating to

the characteristics of the nanoparticles (containing an inorganic core with a targeting moiety)

and their use for therapeutic and diagnostic purposes.

Table 5 Overview of patents held by Nanobiotix

42

Nanospectra

Nanospectra biosciences is a medical device company that is commercializing particle-based

therapies for the selective and precise thermal destruction of solid tumors while minimizing

damage to healthy adjacent tissue. The company was founded on intellectual property from

Rice University and collaborative research with scientists from MD Anderson cancer centre.

Table 6 Overview of patents held by Nanospectra

43

Aduro Biotech

Aduro Biotech was formed in 2008 from a merger between Triton Biosystems, and oncologic

Table 7 Overview of patents held by Aduro Biotech

44

7.3. Companies marketing nanoparticle-based, energy-activated drug delivery.

A recent study conducted by Ernst and Young identified that the majority of nanomedicine

companies were marketing drug delivery technologies. These could be further distinguished

by the nature of the nanoparticle used and whether they were companies adopting the new

technology or founded on these technologies. Although not the scope of this study, a brief

mention of the companies identified using energy-activated nanoparticles for drug delivery

seems relevant if one is to consider a complete spectrum of the industry domain. The

companies mentioned below market complementary technologies to those sought to be

developed through this consortium and may as such represent interesting collaboration

opportunities.

Sirtex

The primary objective of Sirtex Medical is to research, develop, and commercialize effective

treatments for liver cancer using novel small particle technology. They are currently

marketing Sir-sphere, yttrium 90 microspheres for treatment of liver cancer, but have filed a

considerable number of patents relating to the use of magnetizable nanoparticles for

hysteresis-mediated tumor hyperthermia, making it possible (given agreements with

Magforce, see discussion above) for this to become a new market entrant in nanoparticle-

mediated hyperthermia treatment.

Celsion Corp

Celsion corp aims at the treatment of difficult to cure cancers, such as liver cancer and chest

wall carcinoma through the use of heat activateable liposomes. This technology, called

lysolipid thermally-sensitive liposomes (LTSL) differentiates itself from other liposomal

technologies through its unique low heat-activated release of encapsulated chemotherapeutic

agents right at the cancer site. The first in a new generation of liposomes, LTSL will enable

clinicians to target precisely where they want to deliver a high concentration of cancer killing

drug.

First on the horizon: ThermoDox®- doxorubicin dramatically enhanced with LTSL to treat

both hepatocellular carcinoma (HCC, or primary liver cancer) and recurrent chest wall (RCW)

breast cancer.

45

Epitarget

Epitarget is developing technology for local release of cytostatic drugs by means of

ultrasound. Here, therapeutically active substances encapsulated within nano sized liposomes

are administered to the patient and efficiently released at the site of the tumor by exposure to a

defined ultrasound field. The company aims at developing sonosensitive (ultrasound sensitive)

liposomal drug formulations and uses established ultrasound technology to mediate release.

Epitarget’s technology allows administration of higher concentrations of the drugs in question,

in a limited and well-defined area minimizing unwanted systemic toxic effects. Furthermore,

by including an array of substances into the nanoparticles, cancer tumors can be attacked by

several treatment modes simultaneously.

By incorporating contrast agents into drug delivery particles Epitarget has shown that particles

may be tracked and drug release monitored to optimize local medical treatment.

Therm med

Therm med is a research institute currently developing gold nanoparticle or carbon nanotubes

entities conjugated to targeting molecules to detect and attach to local tumors and

circulating/metastatic cancer cells. The targeted nanoparticles are then heated using

radiowaves to induce local heating of the tumor.

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