Six Ways to Fail as an Entrepreneur – Tom Duerig


Dr. Tom Duerig founder of NDC, Nitinol Development Corporation (alternative name, Nitinol Devices and Components), spoke on the topic of entrepreneurship, at www.bio2devicegroup.org event.  Duerig said, while there isn’t a given recipe for entrepreneurial success, there are certainly ways that one can fail and knowing that can help one avoid these common modes of failure.

Duerig began by giving the history of how he found NDC and it begins with the story of the metal, nitinol.  While he worked at Raychem, he realized the enormous potential of this metal.  He formed NDC in 1991, with no patents, no IP, no business plan, no space to work, no products and a tiny sum of $420K raised from individual investors comprising of friends and family.  “What we had was vision”, said Duerig.

So what is nitinol?  Nitinol is a metal alloy of nickel and titanium.  Nitinol exhibits the unique properties of shape memory and superelasticity, along with twinning.  What is extraordinary about nitinol is that its super elasticity effect is within a very narrow temperature range; the temperature inside a human body.  That makes it ideally suited for medical devices, particularly devices implanted inside the body.  Nitinol is ideally suited for stents and guidewires.  Its super elastic nature enables it to not cause trauma and force vessels out.  It is biocompatible and gives exceptional displacement controlled fatigue resistance performance.

1. Entrepreneurship is akin to navigating through a maze of pitfalls and yet if you don’t buy a ticket, you don’t win, said Duerig.  So number one reason for failure is when you have an idea but you don’t take a chance.  At NDC, they had one idea and found one easy product to launch in eye glasses.  That was a wrong product and they were in a wrong business with ultra thin margins.  But they had bought their ticket.

2. It is easy to run out of cash, said Duerig.  Keep the burn rate low and be proud of it.  It is not important to have a fancy facility, when the cash is fast depleting.   Raise more money than you need and then honor cash as if it were your life savings, said Duerig.

3. Next it is important to change and being ready to pivot.  However, when you want to ride a big wave, you need to be 100% committed.  And yet, when you see indications that things don’t seem to go as planned, then it is important to get out fast and catch the next big wave, observed Duerig.  For NDC, a right wave arrived in 1993, and that was the wave they caught; making medical stents.

Even when you catch a good wave, you can’t ride it for too long.  Engineers often love their ideas and don’t know when to quit, said Duerig.  Often there are indications that no matter how committed you are are to your idea, it might not work and it is better to quit.  For instance, when an entrepreneur can’t raise independent money, then it is probably not a viable idea.  At NDC, they were however trapped by their cap table; they had given away too much equity for eye glass business.  So they needed to sort out those details.

4. It is important to not have a divisive cap table.  A divisive cap table leads to lack of unity in governance, and divided governance leads to failure.  Duerig’s advice to the entrepreneurs is that simpler a cap table is, easier it is.  Learn and know everything about liquidation preferences and hire a good attorney, said Duerig.

5. Consider a small win, to be a good win, said Duerig.  He warned against excessive greed.  Durieg advised entrepreneurs to share success, know their limitations, and celebrate the wins that come their way.  When J&J came knocking, NDC accepted the deal and became part of J&J.  Initially, it was hard being a part of a behemoth.  But J&J came to treasure the diversity of thought and considered it a highly successful acquisition.

Durieg helped launch many stents and other medical products, while at J&J.  But a few years later, another wave arrived: another window opened, and Durieg led successful negotiation effort with J&J, for NDC spinout.  NDC now operates as a highly successful, privately held company, with 500 employees, with healthy balance sheet and high profitability.  Durieg remains the CTO, but has recently stepped down as CEO, so we have to watch for the next big wave he will catch.

6. The last point may seem like a no-brainer, but it is perhaps Durieg’s most pertinent advice to entrepreneurs.  He said, luck plays a part and it is possible that luck may not be on your side.  How can an entrepreneur prepare for such an eventuality?  “Don’t give up your day job”, said Duerig.

, , , , , , , , , ,

1 Comment

“Amazon is most customer centric company” – Amit Agarwal, VP & Country Manager, Amazon India – Keynote at 2015 IIT GLC conference


Amazon is the most customer-centric company, said Amit Agarwal, former IITian and now Vice President and Country Manager for India, at IIT GLC conference, in Santa Clara, CA.   Agarwal is responsible for Amazon’s consumer and seller business, in India.  Of his boss, Agarwal said, “Jeff Bezos has genuine customer obsession”.  Transforming the way India buys and sells and in the process transforming lives, is the mission for Amazon, said Agarwal.

Global e-commerce giant Amazon has completed about four years of operations in India.  As Amazon’s Country Manager for India, Agarwal is also responsible for two websites, Junglee.com (launched in February, 2012) and Amazon.in (launched in May, 2013).  Agarwal said that Amazon is relying on effective use of technology to scale massively, while creating a great customer experience.  Amazon is seeking to scale in India, through small entrepreneurs.  First, Amazon focused on bringing sellers to the platform.  Kirana Now, Amazon India’s flagship initiative is creating a lot of buzz.  Kirana Now empowers small mom and pop stores with technology, in processing of orders, so that small entrepreneurs can offer fast and reliable service to the customers.

On the buyer side, Amazon is building solutions that deliver products on the doorsteps of the buyers, with speed and efficiency, said Agarwal.  Seventy percent of Amazon customers expect the product to be delivered by the next day.  Amazon is now giving same day delivery guarantee option and even offers Sunday delivery.  In a massive scale up of online shopping, Amazon has built India’s largest online store with over 20 million items.  

Amazon In is most visited website in India and was voted as most exciting brand by youth.  Amazon is also creating infrastructure to make act of giving easy and trustworthy.  Agarwal said, Amazon’s long term objective is to create a lasting and meaningful impact in India.  

, , , , , ,

Leave a comment

Lessons in Leadership from John Chambers (Cisco): Keynote at 2015 IIT GLC Conference


wpid-20150724_091332-1.jpgHere are some highlights from John Chambers’ keynote.  He advised leaders to be ready to pivot and change, reinvent and stay close to the customers and partners, and get the market transitions right.  He said, the word “linear”, does not exist in startup vocabulary, because startups think exponentially.  Giant corporations need to think exponentially to remain competitive.   In this much hyped era of InternetofThings, Chambers observed that connecting devices is worthless, unless it is connecting right people, at the right time, for the right reasons.

Speaking at IIT conference, on his last day as CEO, at Cisco, Chambers said, as the society is rapidly moving from information age to digital age, those who are slow to change and reinvent, will get left behind.  Some of the top challenges for a corporation to move into the digital age include, deeply entrenched culture that resists change, siloed teams and lack of cooperation between teams, resource constraints, and security concerns.  Here is where a leader’s role is extremely crucial.  To move into and compete in the digital age, corporations need leaders who are world class in operational execution, said Chambers.  Explaining how Cisco pivoted and reinvented itself, Chambers shared that Cisco moved from routing to switches to voice to wireless to storage to telepresence.  Great leaders are great, not because they shine in times of growth and good fortune, but because they handle well the challenges and setbacks, said Chambers.

, , ,

Leave a comment

IIT GLC 2015 Conference – amazing keynotes, awesome panels & limitless networking


IIT Alumni Global Leadership Conference 2015, at Santa Clara Convention Center in Silicon Valley, CA, took place with great fanfare, featured top notch speakers, entrepreneurship focused panels, and network till you drop opportunities.  Board members, CXOs, professors, entrepreneurs and other professionals, whether in academia or industry, found opportunities to galvanize their careers.

The keynotes like Elizabeth Holmes (youngest and self-made female billionaire CEO) at Theranos, and John Chambers, CEO of Cisco (who took the company from $1B in sales to $50B in sales), Pat Gelsinger, CEO of VMWare, and Sal Khan, founder of Khan Academy (http://bit.ly/w2BneL) shared lessons in leadership and making a difference in the world.   IIT alumni speakers included Vinod Khosla (founder of Khosla Ventures and Sun Microsystems); Bharat Desai, founder of Syntel (http://bit.ly/13HmSrQ ), Romesh Wadhwani, founder of Symphony Technology Group and Aspect Development, and Shailesh J Mehta, Managing General Partner at Granite Hill Capital Partners and sponsor of school of management at IIT Bombay.

The conference opened with day one focusing entirely on women in tech.  On days two and three, the conference included a range of thought-provoking panels on diverse topics, centered around themes of entrepreneurship, innovation focusing on inclusivity, and sparking global growth, on giving back, and more.   It was mentioned in the opening remarks that not only great companies are started and run today by IITians but that they take the lessons in leadership to heart and seek to innovate to make a difference in the world.  No doubt, the limitless networking will spark great conversations for further collaborations, to make the world, a better place.

PS – Please check out my opportunities in JOBS category, at this blog.  Currently looking for senior electrical engineer in TX and Clinical Trial Manager in CA.

, , , , , , , , , , , , , , , , ,

Leave a comment

Role of Automated Breast Ultrasound Screening (ABUS) in Early Detection of Breast Cancer


Anupam DattaMajumdar, VP of Engineering, U-Systems at GE Healthcare, talked about the “Role of Automated Breast Ultrasound Screening (ABUS) in Early Detection of Breast Cancer” at www.bio2devicegroup.org event.  “Why is mortality rate among women from breast cancer so high?”, said DattaMajumdar.    Breast cancer is the most common cancer among women, world wide.  About 1 in 8 women globally get breast cancer.  In the US, over 200,000 women are diagnosed and over 40,000 women die each year, from this disease.  Globally, the problem is more severe.  Breast cancer is 5th leading cause of death globally, among women.

Here are some of the top risk factors for breast cancer.  Gender is a factor, as it occurs most frequently among women.  While breast feeding lowers the risk, factors that increase the risk of the disease include, higher age, oral contraceptives, previous breast disease, family history of breast disease, HRT usage, and breast density.  If detected early, breast disease has very good prognosis.  Early detection and using the right tools for early detection is particularly significant in cases of women with high breast density.

Breasts are made up of fat and breast tissue, along with nerves, veins, arteries and connective tissue that helps hold everything in place.  The main chest muscle (the pectoralis muscle) is found between the breast and the ribs..  After menopause (when the ovaries stop producing hormones and a woman stops having periods), the number of lobules decreases and those remaining shrink in size.  The loss of breast tissue during menopause means breast density also decreases and it becomes easier to read the mammograms of women after menopause.  Before menopause however, the breasts have more breast tissue than fat (higher breast density), which makes it more challenging to read the mammograms, particularly in women with denser breasts.  Women with high breast density are four to five times more likely to get breast cancer than women with fatty breasts or with low breast density, said DattaMajumdar.  

Over 40% of American women have dense breasts and for these women additional tools are required for early detection of the disease.  Unfortunately, all states don’t have mandatory rules to notify women of high breast density.  About 47% of American women have no idea whether they have dense breasts and 89% of those that have dense breasts, do not know their breast density level.  Those cancers that are not detected early, are larger, higher grade and have significantly poorer diagnosis.

Women with dense breasts should ask for and receive supplemental screening, said DattaMajumdar.  In addition to routine mammograms, these women should be able to get ultrasound screening.  Mammography is based on attenuation technology where visibility of pathologic conditions depend upon image quality.  Dense breast tissue does not let energy pass through, making it difficult to see differentiate between healthy breasts and tumors.  Sensitivity of mammography is in 85% range but when women have denser breasts the sensitivity can go down to 65% range.

Ultrasound is a better technology to use when screening denser breasts.  Dense breast tissue does not allow for light to pass and mammograms are more challenging but in ultra sound, the return echo makes it easier to identify breast disease.  However, screening by specially trained sonography technicians with labor intensive hand held ultrasound systems, is impractical for broader usage, said DattaMajumdar.  Automated Breast Ultrasound system or ABUS uses high frequency sound waves targeted at the breast, with the scans providing physicians with a 3-D volumetric image of the entire breast.  Currently, there are three systems in use.

Invenia ABUS by GE Healthcare is FDA approved system with software based processing and excellent  user interface to enter the patient data.  Proprietary beamforming technology accompanied by intelligent imaging algorithms, creates focus at every pixel and delivers image of high uniformity, resolution, and reproducibility.  The system is extremely user friendly, with a smooth operator workflow and high patient comfort.  Patient lies down in supine position and non toxic lotion is applied on the breast.  Images generated are sent to the Invenia ABUS workstation for interpretation, enabling fast, quick review.   The 3-D images obtained from ABUS systems allow radiologists the ability to check the denser breasts from a variety of angles, with vastly improved diagnostic ability, said DattaMajumdar.  

The talk was followed by Q&A.

Tags

, , , , , , , , , , , , , , , , , , , ,

Leave a comment

Jobs – July, 2015


.jobs -- Cut To The Chase

.jobs — Cut To The Chase (Photo credit: Wikipedia)

I have new opportunities in California and Texas; many of them are in in engineering in Quality, Manufacturing, and Mechanical and other job openings in Biochemistry, Physiologist with animal surgery experience and in manufacturing and document control of drug delivery type of medical devices.  I will post details as and when I get full descriptions.  All opportunities are for candidates located in the United States.  When sending your resume, please include details on your current compensation and compensation expectations.  Also, include in the email a short summary of your background and your key strengths. Please send resumes to wd_darshana at hot mail dot com.  See below a list of additional opportunities.

Post-docs – Engineering – ME, EE, Biochemistry, Pharmaceutical Sciences – CA & TX
Requires excellent and proven problem solving skills.

Clinical Trial Manager/Sr CTM – Asthma (12-Month Contract) – Berkeley, CA

Overview:  Responsible for managing the full scope of proper study conduct including, but not limited to, protocol development to final report, regulatory filing and/or publications, coordinating cross functional efforts in the administration and progress of Phase 1 to 4 clinical trials.  Additional responsibilities include trial start-up, conduct, and close-out activities in order to achieve program objectives and goals.

The incumbent will use professional concepts in accordance with company objectives to solve complex problems in creative and effective ways.  May determine methods and procedures on new assignments.  Works on complex problems in which analysis of situations or data requires an in-depth evaluation of various factors.  Exercises judgment within broadly defined practices and policies in selecting methods, techniques and evaluation criteria for obtaining results.

Responsibilities:
* Lead clinical trial project execution for asthma programs to ensure that trial timelines, costs, and quality metrics are met.
* Serves as primary contact for functional area representatives in managing protocol execution.
* Manage the financial aspect of clinical trials to ensure accuracy and timeliness of service provider and site payments.
* Forecast and oversee clinical supplies, e.g. study drug.
* Manage study milestones to ensure accurate tracking and reporting of study metrics.
* Oversee ongoing service provider management (e.g., CROs, IVRS, Central Labs), including independent negotiation of scope of work, budgets, performance management, and issue resolution.
* Create and manage clinical trial budgets in collaboration with manager and the Vice President of Clinical Operations.
* May provide study-specific direction and mentoring to CRAs and CTAs.
* Collaborate with Clinical Quality Assurance to maintain quality standards in compliance with regulatory requirements/guidance’s and adherence to SOPs and ICH/GCPs; participate in ongoing process improvement initiatives.
* Manage adherence to ICH/GCP/local regulations.
* Participate in clinical operations initiatives and programs.
* Support the organization in maintaining a work environment focused on quality and that fosters learning, respect, open communication, collaboration, integration, and teamwork.
* Other duties as assigned.

Qualifications:
* Bachelor’s Degree with at least 5 to 8 years of CRA experience for the manager level with at least 1 year of staff management experience.  The senior manager level requires 10+ years of combined CRA and CTM experience and 3 years direct staff management experience is required.
* Experience in inflammatory diseases, specifically Asthma and/or Chronic Obstructive Pulmonary disease (COPD) is required.
* Excellent communication skills to effectively disseminate information within clinical as well as other functional areas as appropriate.
* Experience developing trial plans including developing creative strategies for site monitoring, risk mitigation, trial budgets, site selection, and clinical supplies management.
* Extensive clinical research knowledge and cross-functional understanding of clinical trial methodology.
* Excellent organizational and negotiation skills.  Proven ability in creative problem-solving and possess sound judgment.
* Team oriented and collaborates effectively with the Clinical Operations study team, cross-functional team members, and external partners.
* Proficient computer skills, specifically with Microsoft Office Suite that includes Word, Excel, PowerPoint, and Outlook.
* Working knowledge of MS Project for development and update of clinical study timelines.
* The incumbent in this position must be able to remain in stationary position 50% operating a computer and other office equipment and needs to occasionally move about the office for meetings, to access files, and other office equipment.
* Willing to travel – anticipate up to 25%.

Senior Mechanical Engineer – San Jose, CA
12+ years of Class III medical device is required, with experience in machining, injection molding etc.

Biochemist – San Jose, CA

Senior Electrical Engineer – Austin/ San Antonio – TX
A company working on innovative range of products, has an immediate opening for senior electrical engineer with class III device experience.  Experience with closed loop, analog design hardware, microcontrollers, actuators  and ultra low power consumption circuit design highly desired.

Key Responsibilities
* Lead Electrical Engineering, primarily for long-term implantable drug delivery devices:
* on R&D- design and development of implantable and associated wearable and external hardware using mixed signal- analog and digital techniques, sensors and actuators and closed-loop control systems
* Manufacturing including process development, qualification and validation, IQ, OQ, PQ, part/component selection, sterilization and packaging development and validation esp for implantable electronics
* Develop Class III implantable electronics to be compliant with regulatory and QA standards (FDA and ISO), as well as be power-efficient, reliable for multi-year operation and pass EMI/RFI, be hermetically sealed and packaged and interface with rest of electronics systems for developed products
* Establish reliable suppliers and partners for manufacturing
* Work in a matrixed and multidisciplinary organizational structure to support multiple projects and technologies following appropriate QA system for each segment
* Document work output and use project and organizational documentation systems, including electronic systems
* Plan for and support existing and projected growth of the company.

Key Qualifications
* Designed and implemented electronics mixed-signal hardware, firmware and software for implantable medical devices and drugs. Combinatorial device and Class III experience desirable. 10-15 15 years desirable
* Bachelor’s degree in Electrical Engineering or in an equivalent field required
* Led and grown EE groups with a hands-on, leadership- by-example approach
* Demonstrated working experience and accomplishments with electronics hardware and software- analog/digital, sensors/actuators. Developed, selected and qualified sensors for both implantable device function and for measuring physiological parameters
* Familiarity and experience with other implantable device components such as connectors, leads, cables, interconnects, headers, electronics packaging, communication protocols and standards. Real-time microcontroller programming a plus.
* Excellent and demonstrated grasp and use EDA tools: sensor/circuit design, simulation, layout. Hands-on re: circuit and system prototyping and development
* Developed and implemented manufacturability, and related process flows and controls. Selected and qualified vendors for manufacturing Class III implantable device electronics.
* Working knowledge of biomaterials, drugs, drug delivery, and mechanical technologies in support of multidisciplinary teams: engineering, biological, manufacturing, regulatory, intellectual property, clinical and business.
* Strong technical and hands-on skills with demonstrated ability to provide solutions to a variety of technical problems of varying scope and complexity
* Analytical data-driven problem solver and team player, organized and an excellent communicator
* Supported multiple complex projects in a start-up environment: able to prioritize.

Key Job Parameters
* Full-time position located near Austin/ San Antonio, Texas
* Some travel (~10%) may be necessary to meet job responsibilities
* Report to VP, Product Development

Senior Mechanical Engineer – San Jose, CA

This is an exciting opportunity to work at grounds level with a veteran leader, in innovative drug delivery space.  Minimum 10 years of medical device experience is required.

Opportunities in Berkeley, CA

If you are interested in any of the opportunities below in Berkeley, CA then send me an email with resume and I will be happy to share more details.

BioChemist – San Jose, CA
Scientist I-III, Potency Assay Development – 6-12 month contract
Scientist I/III Protein Analytics (Contract 6-12 months)
Senior Manager / Associate Director, Regulatory Affairs (Clinical)
Director, GxP & Research Applications
Director, SG&A Applications (Finance, Supply Chain, HRIS, and Reporting Systems)
Director/Sr. Director Corporate Communication
Medical Writing QC Reviewer – 12 month contract (x2)
Clinical Trial Manager/Sr CTM – Asthma (12-Month Contract)
Copy Editor – 6-12 month Contract
Director/Sr. Director, Marketing
Laboratory Assistant
Vice President and General Counsel
Sr. Director, Quality Assurance – Commercial
Director/Sr. Director,Quality Assurance, Development
Specialist/Sr. Specialist/Manager – Quality GCP Compliance
Post-Doctoral Fellow (Senior), Analytical Development – Protein Analytics and Characterization

, , , , , , ,

Leave a comment

Changing World of Medtech Investors (includes Software, Big Data, Mobile, Biotech & more) – 2015 WSGR Conference


While there has been a decline in traditional medtech investments, non-traditional investors are investing in new and emerging areas, in medtech.  Software and IoT investors are interested in containing hospital costs and increasing operational efficiency in healthcare institutions.  Biotech investors are interested in alternative therapies, and internet investors are looking at ways to change the way devices are sold and big data investors are looking at opportunities to contain disease outbreaks and better manage large disease populations.  International investors are tapping US expertise to build medtech businesses at home.

A panel at WSGR 2015 Medical Device Conference, moderated by Uday Kumar, Founder and CEO at Element Science Inc., addressed the changing world of medtech investors.  Joining Kumar on the panel were Tom Rodgers, SVP & Managing Director at McKesson Ventures; Andrew Atwell, Principal at Global Innovation Center, Strategic Investments Group; Asha Nayak, Global Medical Director at Intel Corporation; and Conrad Wang, Senior Director of Corporate Development at Medtronic.  Below are some highlights from very interesting panel discussion on changing face of medtech investment.

According to Wang, Medtronic vision is to be a collaborative solution provider in healthcare, with a specific focus on new therapies and geographic diversity of emerging markets.  His advice to entrepreneurs, “focus on how your solutions can create value”.  Instead of being enamored by a technological enhancement, entrepreneurs should keep in mind the impact that the new breakthrough may have on the stakeholders in the healthcare delivery chain. Due to a combination of factors, chronic conditions are increasing globally.  Medtronic looks for opportunities that would enable healthcare providers from engaging in episodic care of chronic diseases to providing continuous care.

Atwell said there are numerous opportunities in the Big Data space, particularly in consumer generated data.  “Our main driver of revenue are mobile devices”, said Atwell.  There are also many challenges.  For instance, it is challenging to get accurate data and see meaningful trends.  It is also a challenge to understand early on how large the market might be and how quickly adoption may happen.  Atwell said his group invests in early and seed stage to A and B rounds and typically invest from $250K to $3M, in any given opportunity.  “We focus on building collaboration among experts from data analytics, health IT, and workflow efficiency”, said Atwell.  He further observed, “additionally, we also look at behavior change space since there is so much access to individuals through their mobile devices”.  Even if they may not help exert deep influence and impact in changing behaviors, mobile devices can exert significant influence over much larger population and can be an effective behavior change tool, said Atwell.

According to Nayak, Intel approach is to provide a piece of healthcare solution that fits in enhancement of health and quality of life, while keeping in mind TCO or total cost of ownership, in healthcare.  Her advice to entrepreneurs, “you should know if you are able to provide a piece that will fit in total solution, even if that may be a few years later”.  From consumer devices, typically wearables, an entrepreneur should be able to harness value in a trustworthy manner.  There are some key questions that an entrepreneurs must ask. 1) Is the data trustworthy, not just in accuracy, but can it be consistently used by the right person?  2) With wearables, one needs to add unequivocal value and discern it from gobs of data.  3) An entrepreneur must consider how it will fit into the current workflow without adding more time to the system.  Entrepreneurs often don’t get this piece, said Nayak.  4) Security of data is critical.  Anytime data needs to be securitized, any time data moves, Intel makes money on it, said Nayak.  5) How is the cost and care impacted through wearables.  Nayak said, Intel is interested in building ecosystems and platforms around the notion of building long term improvement in healthcare, at lesser cost.  Intel invests in all stages from seed to commercialization.   “My group is interested in partnership, and all of our investment is strategic”, said Nayak.  Many areas of interest include, telemedicine, patient management of telemedicine, management of chronic and acute care and also precision medicine, genomics, and analytics that can extract data, said Nayak.

According to Rodgers now the focus is on whether or not an entrepreneur can you navigate the carpteted area of hospitals and provide actual solution that makes a difference.  His advice to startups is to position devices as service.  Device can also be a powerful tool to capture data to ultimately keep people healthy, said Rodgers.  However, average provider does not have the time or the training to deal with the deluge of data.  In order for the data to become actionable, we may need a whole layer sitting in between the patient and the provider, monitoring the datasets, observed Rodgers.  He also advised that entrepreneurs may focus on emerging growth areas and shift to models that enable direct consume care.  We focus on strategic areas, not tactical, said Rodgers.

, , , , , , , , , , , , , , , , , , , , , , ,

2 Comments

Anti-angiogenic/ Anti-Vasculogenic Therapy for Triple Negative Breast & other Cancers


Rathin Das, Founder and CEO of Synergys Biotherapeutics talked about antibody fusion therapy for cancer treatment at http://www.bio2devicegroup.org event.

Synergys is a preclinical stage biotherapeutics company, developing polyfunctional antibody drugs.  It has established an antibody-linked biological payload system called Antibody-Targeted Anti-vasculogenic Payload (A-TAP). The Company’s most advanced product candidate generated from this system is Anti-EGFR-TAP that is being developed as a new generation anti-angiogenic/anti-vasculogenic biotherapeutic for Triple Negative Breast Cancer (TNBC) and other EGFR+ malignancies.

Angiogenesis is the development of new vasculature from preexisting blood vessels and/or circulating endothelial cells, and is essential for neoplastic proliferation, progression, invasion and metastasis. VEGF (vascular endothelial growth factor), PDGF (Platelet-derived growth factor ), bFGF (basic fibroblast growth factor) are among the most prominent of various growth factors and their signaling pathways that support angiogenesis. Due to the commercial success of the anti-angiogenic antibody drug bevacizumab (Avastin®) by Genentech/Roche, the field of angiogenesis has been generating significant interest as potential target for possible anti-cancer therapy. Bevacizumab is an anti-VEGF MAb which blocks angiogenesis by inhibiting VEGF-A . The MAb interacts nonselectively with its receptors VEGFR1 and VEGFR2.

However, bevacizumab suffers from several safety and efficacy issues, despite its approval for various cancers, including colorectal, renal, cervical carcinoma, glioblastoma, and head and neck and others. It failed to delay the growth of metastatic breast cancers, failed to improve the quality of life of the patients, and its side effects were significant, leading to reversal of the drug’s FDA approval in 2011. Another anti-angiogenic MAb , Ramucirumab (Cyramza) from ImClone, (recently acquired by Eli Lily), targets VEGFR2, and has been recently approved. Ramucirumab has been approved for gastric cancer and NSCLC, but it failed at clinical Phase III for metastatc breast cancer.

Earlier to the development of bevacizumab, Endostatin, a 20 kDa fragment of collagen XVIII, was identified as a naturally occurring inhibitor of endothelial cell proliferation in vitro and angiogenesis in vivo. Although highly efficacious in decreasing tumor burden in animal models, and safe in humans in very high doses, no consistent evidence of antitumor activity for recombinant human endostatin (huEndo) was observed in human trials. Several explanations have been advanced for huEndo’s efficacy failure in humans, including its rapid clearance, low potency and sub-optimal presentation as the monomeric form . Despite these limitations, a proprietary formulation of endostatin (EndoStarÒ) has completed Phase III and IV testing and is now approved in China, providing further evidence of its safety and potential for efficacy, said Das.

Synergys is utilizing an anti-EGFR monoclonal antibody as a targeting domain to facilitate the delivery of a mutant form of human endostatin, huEndo-P125A (where Alanine substitution of Proline 125, significantly increases anti-angiogenic potency of endostatin), as a biological anti-angiogenic payload, for the treatment of cancer. Most importantly, unlike earlier failures of endostatin used as an anti-angiogenic in clinical trials, where monomeric form of endostatin with N-terminal amino acid deletions was used, “ in our approach a ‘dimeric’ fusion of a full-length endostatin-P125A mutant to a targeted antibody is utilized”, said Dr. Das. The “dimeric”endostatin-P125A generated by linking two molecules of endostatin-P125A to two heavy chains of an antibody molecules shows excellent inhibition of endothelial cell angiogenesis and profound inhibition of vasculogenic mimicry or VM. VM is the formation of an alternative tumor vasculature assembled directly from tumor cells and not from vascular endothelial cells.

Synergys is developing Anti-EGFR-TAP for the treatment of Triple-negative breast cancer (TNBC), which is an especially deadly subtype of breast cancer, said Das. It comprises approximately 15% of newly diagnosed breast cancer and is overrepresented in young women, in patients with BRCA1/2 mutations and in women of African ancestry (1). At present, TNBC has the poorest survival outcome of all breast cancer subtypes. TNBC lacks the three most commonly targeted receptors in human breast cancer: the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)/neu. However, the expression of epidermal growth factor receptor 1 (EGFR, HER1) is reported in greater than 60% of TNBC. Although no approved targeted therapy is currently available for the treatment of this highly aggressive subtype of breast cancer, several recent clinical studies involving agents for DNA repair by poly (adenosine disphosphate-ribose) polymerase (PARP inhibitors) have shown promising results in some BRCA1 and BRCA2 mutated TNBC patients. However, the role of PARP inhibitors in unselected TNBC patients is still uncertain and newer more effective targeted therapies are urgently needed for TNBC .

In addition to tumor induced angiogenesis, TNBC readily exhibits VM. Indeed Anti-EGFR-TAP demonstrated excellent inhibition of endothelial cell angiogenesis and profound inhibition of VM of TNBC cells.  Anti-EGFR-TAP treatment also showed significant inhibition of growth of triple negative breast cancer xenografts relative to those treated with cetuximab (Anti-EGFR MAb).  Various published studies have shown that none of the approved angiogenesis inhibitors inhibit VM. Indeed, not all anti-angiogenic antibodies show anti-VM activities. To this end, in a head to head comparison, three other anti-angiogenic antibodies were negative in VM assays relative to Anti-EGFR-TAP. The inhibitory effects of Anti-EGFR-TAP for both angiogenesis and vasculogenic mimicry , therefore, is both interesting as well highly promising as a potential drug for progressive cancers, said Das.  Further Das observed, it is important to inhibit both angiogenesis and VM, not just angiogenesis, to inhibit overall tumor growth.

Synergys is attempting to collect more safety and efficacy data with significant animal studies and also looking at other EGFR+ malignancies . Das said that the A-TAP technology is a new generation of cutting-edge biological payload system that is capable of generating highly efficacious polyfunctional biotherapeutics , with multibillion dollar market potential.  Currently, they are seeking financing for rapid product development. The company is also open to negotiations around partnering and structuring deals around out-licensing business model.

(Edits by Rathin Das).

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,

Leave a comment

Innovative Deal Structures in Medtech Financing (2015 WSGR Med Device Conference)


WSGR 2015 Medical Device conference, focused on understanding the challenges facing the medical device industry, and highlighting the emerging strategies to navigate the new and complex world of medtech. Eminent team of panelists discussed “innovative deal structures” at WSGR medtech conference, in San Francisco.  The panel was moderated by Scott Murano, Partner at WSGR and panelists included Justin Klein with New Enterprise Associates, Evan Norton, Divisional VP at Venture Investments, Abbott Ventures and Mir Imran, Chairman and CEO at InCube Labs.  The panel shared insights from their recent experiences with corporate partnering transactions.

Justin Klein at NEA, with $3.1B fund, focuses on medical device, healthcare technology and biopharmaceutical investments.  Recently NEA funded three medical device companies, all of them in Atrial Fibrillation space.  “Scarcity of assets in AFib category positioned AFib as a very attractive category”, said Klein.  NEA was a strategic investor alongside others, including Abbott Ventures, in its more recent financing of Sunnyvale based VytronUS, with a proprietary cardiac imaging and ablation system to treat atrial fibrillation and other arrhythmias.  Although NEA funds companies from early stage, VytronUS is couple of years away from commercialization, said Klein.  NEA looks for interesting opportunities to syndicate with a broader variety of partners.

Evan Norton said his job at Abbott Ventures is to go out and find new business that Abbott can enter into.  Abbott Ventures focuses on emerging medical technology companies that have the potential to provide long term strategic growth options for Abbott.  Mostly AVI looks for early stage opportunities and makes it possible for early stage companies to gain critical access to capital, in return for bigger equity stake.  “Our job is to identify the next Spinal Modulation earlier”, said Norton, referring to Mir Imran’s company that was recently acquired by St. Jude.  AVI does not move to non-buying term sheet phase earlier, in the process.   “About a 4th of the capital in our syndicates, comes from China”, said Norton.

Among corporate venture funds, Abbott Ventures tends to be highly creative in putting together early stage deals.  AVI focuses on medical devices, drug/ device combinations, diagnostics and unique drug delivery technologies.  An absolute key aspect of putting together a deal is flexibility on both sides, said Norton.

Mir Imran, Chairman and CEO at InCube Labs, also runs VC fund at InCube Ventures, along with an online crowd funding platform at Venture Health.  Currently, there are about 9 companies that are incubated at InCube Labs.  The Spinal Modulation deal happened with SJM “because SJM was creative in putting together a deal they could live with and we could live with”, said Imran.  Most recent buzz has been around Imran’s company, Rani Therapeutics, which has developed a technology to convert injectable biologics (such as insulin and Humira) into pills, allowing millions to escape the needle prick.

“Rani has a powerful platform and many large pharma companies are talking with us to convert their injectable drugs into pills”, said Imran.  According to recent announcement, Novartis has joined previous investors Google Ventures, InCube Ventures and Venture Health, in a Series C round of more than $25M and similar deals are in the works with other investors.  The deal will allow Rani to evaluate Novartis molecules on the new platform, with equity investment and all expenses for testing of the molecules to be paid by Novartis, said Imran.  Imran avoided entering into license negotiations, at this stage.   “If the technology delivers expected results with Novartis molecules, then we can sit down and put a licensing deal at a later time”, said Imran.   

How has Imran managed to create mutually beneficial conditions for deal negotiations, with large pharma?  “From small company perspective, I don’t like to give away rights too early”, said Imran.  Most of Imran’s companies come out of R&D at InCube Labs.  “We keep our burn rate low and keep a relentless focus on execution”, said Imran.  

, , , , , , , , , , , , , , , , , , , , ,

Leave a comment

2015 WSGR Medical Device Conference – Venture Capital Today


Wilson Sonsini Medical Device conference, this year, focused on understanding the challenges facing the medical device industry, and highlighting the emerging strategies that counterbalance the new and complex world of medtech. During the sold out dinner interview, on the night preceding the conference, Steve Blank joined David Cassak, in conversation on Lean Launch Pad approach to building Medtech startups. Here is link to my previous write-up on Lean Launch Pad http://bit.ly/11yF4EM .

Venture Capital Today – Panel

The conference began with a panel moderated by Casey McGlynn, with medtech investors sharing their insights on investing in the changing times. Early stage life science companies emerge in an environment of ever shrinking pool of investors. McGlynn was joined by Steven Hochberg from Deerfield Management, Alan Kaganov from US Venture Partners, Evengy Zaytsev from RIM Partners and Eric Milledge from Endeavour Vision Ltd.  Prolonged regulatory and reimbursement challenges and the need for real sales traction to attract interest from potential acquirers has made early access to large capital, imperative. Acknowledging the changing reality, the panel noted “our filters are tighter”.

However, the conversation was not all bleak. The panel also observed that “if you have a solution and a strong product, and strong IP, then it can’t fail”. Acknowledging the changing reality, it was also noted that partnering has become an important element of the new medtech world and financing through series A, B, C, D, E is not going to happen anymore. It was acknowledged that majority of the funds for future innovation are likely to come from outside the US. One of the panelists was bullish on medtech, and observed that people’s fundamental desire to live longer and healthier, is a huge driver for medtech innovation, and advised startups on having clear and strong IP position. “If you don’t have strong IP, you don’t have a business”, he said. Underscoring the importance of a good team, he further observed, “You have no room for a weak link, in a startup”.

Stay tuned for other blogs on the conference, in the coming days.  Medtech Jobs are posted at the link http://bit.ly/1EXGy7T .

, , , , , , , , , , , , , ,

Leave a comment

Follow

Get every new post delivered to your Inbox.

Join 2,458 other followers

%d bloggers like this: