Oncolytic virotherapy – a new weapon in the war against cancer?

Genetically engineered viruses capable of selectively targeting cancer cells while leaving healthy cells unharmed are gaining popularity as a promising oncolytic treatment. San Francisco-based biotech firm Jennerex debuted JX-594, a genetically engineered virus that can selectively target tumors and cancerous cells without affecting healthy tissue. JX-594, derived from a virus strain once used in the smallpox vaccine, attacks and lyses cancerous cells after viral replication, reducing blood supply to the tumor and increasing the body’s immune response. Administered intravenously, JX-594 has the potential to prevent metastasis. Back in May, Jennerex announced the success of its Phase I clinical trials and has partnered with French biopharmaceutical firm, Transgene, for Phases IIb and III. JX-594 is currently being tested on patients with liver cancer and metastatic colorectal cancer (mCRC). Transgene is set to receive European commercialization rights, and hopes to market the drug by 2015. Jennerex is working on additional viral strains targeting other cancers, including pancreatic and prostate cancers.

In related news, CZ BioMed, a Florida startup, recently introduced RVLYSIN, a line of oncolytic viruses targeting various cancers. RVLYSIN is a genetically engineered virus derived from the common cold virus. Early results demonstrate that RVLYSIN localizes to tumor cells and kills them primarily through lysis. Lysis triggers a subsequent systematic anti-tumor response, including attracting high local concentrations of interferon (IFN) to protect healthy cells by limiting viral replication. CZ BioMed also claims RVLYSIN can induce apoptosis in tumor cells. Currently in the pre-clinical stage, CZ BioMed demonstrated PANRVLYSIN (its product targeting pancreatic cancer) is well tolerated in mice. The company is seeking interested partners to initiate Phase I trials.

Although oncolytic viruses promise minimal side effects (similar to a cold) and potential to replace chemotherapy, concerns remain over dosage and efficacy. JX-594 and RVLYSIN share the same primary mechanism – lysis. And cancer cells are a preferred host due to their rapid growth and vulnerability to a second infection (for certain types of cancer). At this early stage, results have largely been inconclusive, as researchers continue investigating the relationship between therapeutic effect and level of viral replication. Another key concern is the possibility of the tumor returning if the immune system manages to fight off the virus. Other oncolytic viruses in development – including Amgen’s OncoVex and Oncolytics Biotech’s Reolysin, both currently in Phase III trials – require direct injection into the tumor and additional chemotherapy, respectively. Clients interested in oncolytic virotherapy should stay tuned as we reach out to Jennerex and CZ BioMed for full briefings.

The Lux Top 10: Q3′ 11

In the third quarter of 2011, Lux Research analysts profiled 286 companies in 11 different emerging technology sectors. Here are the 10 they thought were the most compelling. Some are already enjoying great commercial success, and should continue to do so. Others are promising upstarts that could yet fail but have the potential to achieve great things. Let us know your thoughts and watch this space for the next quarter’s results.

1. Semprius – Positive – Solar systems

If the company can maintain high yields in automated mass manufacturing, it will have the market’s most attractive high-concentration PV module.

2. Qingdao Institute of Bio-energy and Bioprocess Technology, Chinese Academy of Sciences – Positive – China Innovation, Alternative Fuels

With multinationals such as Boeing and Shell undertaking joint research partnerships, Qingdao has emerged as a leading Chinese institute in alternative fuel technologies.

3. Ice Energy – Positive – Green Buildings

As a complete solution provider of ice-based thermal storage systems for peak-demand load shifting, Ice Energy has secured valuable channels to market via partnerships with Trane and Carrier.

4. Oxis Energy – Wait and See – Electric Vehicles

Although still too early in development to declare success, next-generation energy storage solutions are potentially disruptive in the transportation market, and UK-based Oxis Energy could be one of the first to reach market with its lithium-sulfur battery.

5. Aerogen Therapeutics – Strong Positive – Targeted Delivery

Aerogen is targeting both health and consumer applications, as well as the medical device market, with a versatile electronic micropump technology that aerosolizes liquid drug formulations.

6. Modumetal – Strong positive – Advanced Materials

This leading developer of electroplated metal coatings has shown great savvy in procuring high-profile customers and partners across the aerospace/defense, automotive, and oil and gas industries, despite long development lead times.

7. Sensus – Strong Positive – Smart Grid

A dominating player in the North American advanced metering infrastructure market that spans the entire value chain.

8. Breivoll Inspection Technologies – Wait-and-see – Water

Technology adoption in the $20 billion water infrastructure repair market is notoriously slow, but is inspiring innovations from the likes of Breivoll, which has developed a nondestructive metal water pipe profiling to locate and fix water system weak points before they cause blowouts.

9. E-Ink – Strong Positive – Printed Electronics

Having captured most of the market for e-reader displays with its electrophoretic film technology, E-Ink is looking to other applications as the leisure e-reader market saturates.

10. Avantium – Positive – Bio-based Materials and Components

With its novel furanic platform, Avantium is pushing towards the polyester markets and fanning the flames of the drop-in versus novel chemical debate.

Mark Bunger

VC contributions decline as overall investment in targeted delivery accelerates past $4 billion

Funding for targeted delivery and formulation technology companies exceeded $724 million in 2010, bringing total investment since 2000 to $4.1 billion. During this period venture capitalists have represented a notably declining share of overall investment. After peaking at 51% in 2005, the percentage that venture capitalists (VC) contributed dropped to just 22% last year. Meanwhile, as this week’s graphic illustrates, the venture funding that was invested over the past several years increasingly went toward later stage rounds.

Between the years 2004 and 2010, a total of 96 VC financing rounds took place in the targeted delivery space. The year 2007 marks the peak annual total of twenty VC-backed transactions, half of which were A/seed rounds of financing averaging $6.9 million.

The following year, 2008, the number of A/seed rounds dropped to six, but their average value rose to $9.3 million. Even so, later stage investment was already outstripping A/seed funding – both in terms of the number of deals and their average value. The year 2008 saw five B rounds averaging $15.4 million, three C rounds averaging $7.7 million, and one D round worth $21.9 million. Only one A/seed round was secured in 2009 (for $12 million), but there were five B rounds averaging $10.1 million and three C rounds averaging $35 million.

Last year, A/seed rounds disappeared altogether. Of the thirteen venture deals made in 2010, four B rounds and seven C rounds went to companies like Amplyx*, which received $1.5 million in Series B financing for its chemical modification technology, and polymer nanoparticle company Cerulean Pharma*, which received $24 million in Series C financing in November.

* Client registration required.

Source: Lux Research report “Homing In on Targeted Delivery Investment Opportunities.”

 

Chananit Sintuu

Electronic tattoo merges art, electronic sensors, and diagnostics industries

Researchers have developed an epidermal electronic system (EES), that resembles a temporary tattoo, allowing doctors to diagnose and monitor certain conditions noninvasively. The details of the device and study were co-authored by researchers at the University of Illinois at Urbana Champaign, Northwestern University, Tufts University, the Institute of High Performance Computing at A*Star in Singapore, and Dalian University of Technology in China. They published their results in a recent issue of Science.

The EES technology integrates sensors, light-emitting diodes (LEDs), a variety of circuit elements, wireless power coils, and devices for radio frequency communications onto the surface of a 30-micron, gas-permeable, polyester-based elastomeric sheet produced by BASF. The solar-cell-powered device is “barely noticeable,” measuring less than 50 microns thick (slightly thinner than a strand of hair) and weighing just 0.09 g. It uses conventional electronic materials (such as silicon and gallium arsenide) in the form of nanoribbons and nanomembranes for the functional parts – mainly the semiconductor, sensor, and insulator components – and forms a “stretchable net” that can move with the skin.

The EES doesn’t require any adhesives. Instead, it relies on van der Waals forces (weak forces between molecules, atoms, and surfaces) to form molecular interactions between the skin and the polyester layer. A water-soluble polymer sheet, made of polyvinyl alcohol, is used as support to mount the system onto the skin in a transfer mechanism similar to that of temporary tattoos.

Although the researchers were able to show that the EES device could measure electrical activity from the heart, brain, and skeletal muscle, the technology is still relatively early-stage and “not [yet] fully integrated.” Several concerns may prohibit its long-term use. For example, the skin’s natural exfoliating activities currently limit the EES lifespan to two weeks at most, which makes it less ideal for long-term monitoring use. Sweating and sensor damage due to stretching may also impact the results, and need to be addressed. And the cost of fabricating such fine and complex structures may be prohibitive for a disposable device. Nevertheless, the convergence of the electronics industry with the medical industry is becoming more* and more* apparent, and clients focused on traditional electronics applications should take note.

* Client registration required.

Jaideep Raje

Finding the synergy between the boiler room, boardroom, and break room

The October print edition of Oregon Business (OB) raises the all-important question: “Are green buildings really saving energy?” It draws upon the experience of Portland, Oregon to evaluate whether or not incentives for energy-efficient buildings translate into buildings that meet expectations once they are occupied. In the article, the city’s green building manager, Alisa Kane (whose office is a part of the City of Portland’s Bureau of Planning and Sustainability), points to this troubling statistic:Over the past 15 years, while the energy codes for buildings have become more stringent, the actual energy use has not gone down. The culprit, she says, is operations and behavior of the occupants.

Ms. Kane’s point is well taken, and speaks to a broader concern in the green buildings regulatory community. While regulators are able to monitor and effectively assess if a LEED-rated structure meets pre-construction expectations during design and early post-occupancy evaluations, the process falters when occupants bring in “plug loads” that increase energy use beyond the building’s design expectation. This problem is magnified with the proliferation of plug-and-play devices (e.g. mobile phones, music players, mini-refrigerators, computers, space-heaters, etc.) that are ubiquitous in most offices and commercial spaces today. This disconnect prevents regulators and tenants from getting an accurate idea of the building’s true energy performance.

In the short term, the solution is two-pronged: First, the U.S. should follow the model established by the European Commission through its Directive on Energy Performance of Buildings (2010/31/EU, 19 May 2010). This directive states that all building owners must show energy performance certificates to prospective buyers or tenants when constructing, selling, or leasing property. Although overall, the U.S. lags Europe on this front, individual cities like Seattle, San Francisco, Austin, and Washington, D.C. have enacted similar laws over the past few years. Such policies impose a true market value on building efficiency, and provide a benchmark for improvements. However, predicting energy requirements is easier said than done. As the Oregon example shows, building owners and managers are loathe to accept such legislation since they see it imposing a penalty on them for the truancy of their tenants.

Second, when commissioning a building, set more realistic design parameters that account for the true expected in-use profile of today’s tenants. However, this approach has its own issues. Not only does it not dissuade ballooning energy consumption, it also risks over-compensation in design affecting the cost-optimality/profitability of the project.

Both of these measures are only a short- to mid-term fix. The longer-term solution is fundamental behavior change on the part of building owners and the corporate managers and employees on the tenant side, leading to an integrated decision on managing energy use. In short, as one respondent in the OB article pointed out, we need “a synergy between the boiler room, boardroom, and break room.”

This issue, and its likely solutions, augurs a few trends for clients operating in the green buildings space. Demand for energy audits will increase and, depending on region, they could be either voluntary or mandatory. Expect enhanced prospects for companies like CADmeleon*, kWhours*, and FirstFuel*. Also, there is a clear need in the marketplace for companies offering a BEMS-integrated services package.Players active in the domain like IBM*, Cisco*, Echelon*, and Lucid Design Group* provide parts of the whole, but often lack in the understanding/management of the fundamental human element of this puzzle. Expect increasing incorporation of new ideas (e.g. OPower*), and more acquisitions by larger players looking to obtain this missing piece.

* Client registration required.

Kevin See

Ranking Li-ion battery developers on the Lux Innovation Grid

Li-ion batteries are the technology of choice for the first generation of all-electric and plug-in hybrid electric vehicles, and the subsequent hype has attracted an increasing number of competitors to an already crowded market. Soon, it will be impossible for all of these companies to survive, making strong partnerships a necessity. This week’s graphic illustrates how developers of Li-ion batteries compare on the Lux Innovation Grid, helping to identify which will make the strongest potential partners as the electric vehicle market matures.

LG Chem Power clearly leads the pack, standing out even amidst its competition in the graphic’s Dominant Quadrant. A subsidiary of LG Chemical, LG Chem owes its strong technical value to its high-energy lithium-manganese-spinel-based cells and strong cycle life, both of which come at costs that are among the most competitive in the market. Its multitude of supply partnerships with the likes of GM, Eaton, and Ford, however, justify the company’s strong business execution score.

Significant enhancements in specific energy and a commensurate reduction in cell costhas garnered Envia Systems the attention of major investors including GM, Asahi Glass, and Asahi Kasei. Yet serious competition remains for Envia in cathode materials, including two major corporations in BASF and Toda Kogyo licensing the same Argonne National Laboratory technology that Envia’s materials are based on.

China is home to a number of top contenders, thanks to the Chinese government’s desire to keep the electric vehicle value chain inside China’s borders (Client registration required.). But batteries from China BAK, BYD, and China Aviation Lithium Battery (CALB) are undifferentiated technologically, and may not share the quality of cells manufactured outside of China.

Source: Lux Research report “Using Partnerships to Stay Afloat in the Electric Vehicle Storm.

Reka Sumangali

Siemens’ low-energy desal system – Deal or no deal?

At Singapore’s International Water Week conference in July, Siemens announced the results of its low-energy electrodialysis desalination system. The project for the Singapore government targeted energy usage of just 1.5 kWh/m3, which is near the theoretical limit* for desalination technology. Siemens operated the Singapore plant for the last three years, and during that period reduced its energy consumption to 1.7 kWh/m3. However, they explained to Lux that the system’s opex and capex still needed improvement to be truly competitive with seawater reverse osmosis (RO). Contractually, failing to reach the 1.5 kWh/m3 target holds no penalty. Siemens said that it had completed optimization of the plant, but added that it’s still working in the lab to reduce costs. It aims to unveil the product of that work in 12 months to 24 months.

In learning more about this technology, some things stood out to us. First, the system’s membrane is 10 times more expensive than the threshold for cost effectiveness. This is especially striking given that it’s an off-the-shelf product with no modifications. In addition, the system achieved a relatively low freshwater recovery of 35%. Although electrodialysis systems are not expected to require as much pretreatment as reverse osmosis, this system operated behind an existing ultrafiltration membrane, signifying a best-case scenario. Further, this solely Siemens-driven effort created more than 100 invention disclosures, suggesting the project is at least as much research as development.

While Siemens has proven it is possible to approach the theoretical limits of energy use for desalination using electrodialysis, it has yet to prove it can do so in a cost effective way. Without this, it is unlikely this system will see the widespread implementation implied from the buzz surrounding its press release.

* Client registration required.

Steven Minnihan

Saft’s defensive strategy against Johnson Controls paying early dividends

Last May, Johnson Controls filed a petition to dissolve its joint venture with French battery-maker Saft. But Saft opposed JCI’s pressure to move the JV outside the original scope of automotive battery applications and into the energy-storage market*.Saft’s resistance appeared to be vindicated in late July, with the announcement of two grid-storage projects in France totaling nearly 6 MWh of advanced lithium-ion storage.

In the first, Saft will deploy 500 Li-ion storage units of 4 to 8 kWh for the Millener Project to smooth out energy supply generated from photovoltaic installations being rolled out across several of France’s island territories. In the second, Saft announcedits listing as first-rank partner for 2.7 MWh of energy storage in mainland France’s Nice Grid project, which covers storage applications at origination and distribution substations as well as residential storage. Though energy storage and renewables are typically more cost-effective for island applications such as the Millener Project where a region lacks a robust centralized grid, the Nice Grid project provides evidence that the time is approaching for larger mainland grid storage projects. Both projects not only offer Saft the opportunity to further test and demonstrate the effectiveness of its technology, they also allow it to cultivate relationships with the numerous other project partners, including BPL Global*, Delta Dore, Edelia, Schneider Electric,Tenesol*, the European Regional Development Fund (ERDF), Alstom Grid, and EDF.

Despite its emotionally tarnished relationship with JCI, Saft made the correct tactical move to isolate its strong position in the energy storage market from JCI’s reach into the energy storage arena, which already includes a memorandum of understanding with Hitachi and an endowment for an energy storage program at the University of Wisconsin. It is important to note that, similar to its microgrid project in San Francisco*,Saft’s projects in France are subsidized by government funds,  which indicates indicating that in many applications grid energy storage is not yet market-ready on its own. Nonetheless, if Saft succeeds with its several ongoing energy storage demonstration projects, it should remain a leader in this market over the mid- to long-term.

* Client registration required.

Matthew Feinstein

Setting the record straight on Solyndra

Nearly $1 billion in venture capital funding, a massive U.S. Department of Energy (DOE) loan guarantee, and a disruptive technology tabbed to translate United States clean technology innovation into economic growth have kept mentions of Solyndra alive in the business press and solar industry circles well past its demise. A number of interconnected conclusions have been drawn. Some are true, some are false, others lie in the middle. Among them:

Claim: Unexpected drops in polysilicon prices destroyed Solyndra’s business case.

Reality: Indeed, polysilicon prices falling from the order of hundreds of dollars per kilogram to roughly $50/kg today – and destined to fall further – rippled downstream, allowing module prices to fall from $3.80/W in 2008 to $1.50/W today. However, the drop was hardly unexpected. In February 2009, the Lux Research State of the Market Report “Finding the Solar Market’s Nadir” (client registration required) stated: “…in 2009, securing polysilicon will cease to be a major concern for an industry plagued by module oversupply, and polysilicon prices look ready to fall, even before the material goes into oversupply relative to x-Si manufacturing capacity in late 2009.”

Claim: Chinese manufacturing will always win thanks to significant governmental support.

Reality: While Chinese government support allows for ease in scaling production, it wasn’t a problem for Solyndra. Solyndra set up two fabs – extremely advanced facilities, at that. Fab 2 was constructed with former manufacturing mistakes in mind, featuring highly-automated processes and set to maximize yields and throughput. However, the company’s low yields and high production costs are design constraints – and certainly not borne of a lack of governmental support or competition from industry elsewhere. We warned of Solyndra’s high manufacturing costs over a year ago: “manufacturability proving difficult with low yields, and costs remain very high…positive gross margins a moving target” (see the June 10, 2010 LRSJ – client registration required).  The company’s investors believed it would win, and the loan guarantee program did its job in enabling the company to scale operations, and providing the opportunity for the company to prove its technology a competitive option; failure to do so was the fault of Solyndra alone. States will continue to offer support of the industry domestically, and companies will continue to manufacture in the U.S. – Stion and Calisolar are scaling in Mississippi, while Solopower plans to ramp operations in Oregon.

Claim: The solar industry in the United States is now doomed.

Reality: Just because high-cost players like Solyndra, Evergreen, and Spectrawatt couldn’t survive in the face of falling prices – a necessary step towards achieving grid parity – doesn’t mean the industry will turns its back on U.S. demand. In addition to Stion, Calisolar, and Solopower, downstream participants like SolarCity, SunRun, and Verengo are expanding operations in the U.S. Installers, developers, and integrators are poised to capitalize on U.S. market growth, and in doing so, will succeed where Solyndra failed (see the September 15, 2011 LRSSJ – client registration required).

Separate from each argument about Solyndra’s product or implications for the industry after its fall, is the political matter at hand – with regards to the due diligence performed prior to being granted the loan guarantee in 2009. While this debate is sure to continue well into the 2012 presidential election cycle, keep in mind that Solyndra was a unique, highly-publicized case that suffered from the same market conditions as its peers – but its own inability to compete should not discount the prospects of other U.S. solar players, nor should it be seen as an indicator of the broader demand market in the U.S.

Andrew Soare

Investors pump $930 million into alternative fuel technologies

Graphic of the WeekIn 2010, investors gave $930 million to alternative fuels start-ups, a four-year low. However, investment climbed dramatically to an all-time high of $698 million for companies with flexible technologies that can use a variety of feedstocks or generate diverse end products. Flexibility increases a technology’s addressable market, provides secondary revenue streams, and unshackles technologies from price volatility.

Specifically, synthetic biology start-ups – which develop novel organisms ranging from Escherichia coli (E. coli) to yeast – have attracted the most funding since 2004: $1.84 billion or 28.4% of the total. Investment dipped just 16.7% from $436.5 million in 2007 to $358.3 million in 2009, and investments actually peaked last year at $447.0 million, representing 25% growth over 2009. Driving this growth were companies with novel and flexible technologies to make both fuels and chemicals, such as Solazyme ($60 million Series D), LanzaTech ($18 million Series B), and LS9 ($30 million Series D). Since those 2010 transactions, Solazyme and several other venture-backed companies in the space have launched successful IPOs (Client registration required).

But investors shouldn’t ignore other flexible technologies. Investment in thermochemical processes (pyrolysis, gasification, torrefaction) did not trail far behind synbio. Technologies in this category account for 43.3% of the funding thus far in 2011. Representative companies include Virent and Elevance, whose catalytic processes produce a range of fuels, rubbers, oils, and plastics. Technologies capable of using agricultural, solid, or gaseous waste, such as LanzaTech, GlycosBio, and Ignite Energy, present further opportunities for investors.