New Waves in Biotech – Chinese Bioscience Association Annual Conference Review

The Chinese Bioscience Association (CBA) is a non-profit organization, with a mission to promote education, networking, and community building for life science professionals.

At its recent annual conference in San Francisco Bay Area, an impressive array of speakers discussed new trends, promises, and challenges in the biotech industry.

English: A diagram illustrating the distinction between cancer stem cell targeted and conventional cancer therapies (Photo credit: Wikipedia)

In his keynote address, Dr. Frank McCormick, Professor at UCSF and founder of Onyx Pharmaceuticals, talked about targeted cancer therapies and some of the lessons learned from Onyx.  Almost 30% of all mutated cancers happen in oncoproteins like BCR-ABL and RAS.  In 1994, Onyx initiated a 5 year collaboration with Bayer that led to $25M study for drug development, based on RAS pathway.  Unfortunately, it did not lead to drug leads.  In hindsight, “we realized that it was too early to jump into the pathway based on our feeble understanding of RAS pathway”, said McCormick.  However, Onyx has had several successes, despite the fact that finding new targets has become increasingly difficult, said McCormick.  Sorafenib, a kinase inhibitor, was approved for treatment of renal and liver cancers.  Onyx also has had success in viral therapies.  In 2009, Onyx sued Bayer, its longtime partner, and won the lawsuit.  Removal of the “change of control” clause in the original collaboration agreement, in favor of Onyx, has resulted in Onyx going from a $10M company in 1994 to $10B company in 2014.

English: Listeria monocytogenes grown on Listeria Selective Agar (Photo credit: Wikipedia)

Dr. Stephen Issacs, Chairman and Founder of Aduro Biotech talked about the importance of embracing change to keep growing.   Issacs shared his story from 1978 where his career began in psoralen photochemistry and then teaching at UC Berkeley.  In 1991, he found Cerus Corporation, a biomedical products company commercializing the Intercept Blood Systems.  He raised over $650M and negotiated a $200M partnership with Baxter International and took the company public.  He then found Aduro BioTech.  Here is my previous article on his company Aduro Biotech http://bit.ly/JqDJ3K that uses a bacterial vector, in the form of genetically modified listeria, to stimulate the immune system to fight cancers and infectious diseases.  Issacs also talked about his volunteer work in Kasigau, Kenya through his family non-profit organization, a cause that is very dear to his heart and to which he is highly dedicated.

Kayser-Fleischer ring: copper deposition in Descemet’s membrane of the cornea. These rings can be either dark brown, golden, or reddish-green, are 1 to 3 mm wide, and appear at the corneal limbus. With rare exceptions, they are diagnostic of inherited hepatolenticular degeneration—Wilson’s disease. This 32-year-old patient complained of longstanding difficulty speaking. He also had a tremor. (Photo credit: Wikipedia)

Dr. Chandler Robinson shared his incredible story of how he went from being an undergraduate researcher to becoming a CEO of Tactic Pharmaceuticals, a privately held biotech, in Chicago. Tactic acquires and develops pre-clinical and clinical stage compounds.  Somewhere in between his strenuous MD program at Stanford and pursuing his MBA in UK, Robinson acquired an abandoned drug, Decupratetm, and after couple of years, published his research in Science.  In early 2013, Decupratetm got Orphan Drug Designation from European Commission for treatment of Wilson’s Disease.  Wilson’s Disease is characterized by its disturbed copper metabolism that leads to copper accumulation in the body, resulting in severe disability or death. Tactic Pharma has acquired 3 compounds to date.

Diseases and conditions where stem cell treatment is promising or emerging. (See Wikipedia:Stem cell#Treatments). Bone marrow transplantation is, as of 2009, the only established use of stem cells. Model: Mikael Häggström. To discuss image, please see Template talk:Häggström diagrams (Photo credit: Wikipedia)

At Stanford Cardiovascular Institute (SVI), Dr. Joseph Wu and his team work with iPS cells (induced pluripotent stem cells).   Wu is recipient of several awards and his clinical activities involve adult congenital heart disease and cardiovascular imaging.  According to Wu, iPS will be a game changing platform for drug discovery research.  Familial hypertrophic cardiomyopathy (HCM) is one of the most prevalent cardiovascular disease.  At some point, we should be able take blood and make iPS cells, differentiate them into cardiac cells or other cell types, and expose them to different drugs to find out what would be the ideal drug for that patient, said Wu.  Wu said, it is important to study different ethnicities; different ethnic groups metabolize drugs differently.  CVI has received $20M grant and Wu’s team is trying to create a bank of 1000 cell lines, for drug discovery research.  (iPSCs) seem to have exciting therapeutic implications in regenerative medicine, particularly for myocardial infarction and possibly for neurodegenerative diseases, diabetes and other disorders.  However, stem cell biology is as yet incompletely understood and  some of the challenges include immunogenicity, tumorigenicity and so on.  Drugs can be tested on surrogates of patients, before giving them to the patients, said Wu.

Inhaler (Photo credit: Wikipedia)

Dr. Moninder Hora, SVP at Nektar Therapeutics talked about Nektar’s pipeline and technologies.  Nektar’s technology is based on polymer conjugation platform, said Hora.  Nektar has a robust pipeline of novel therapeutics and Nektar also partners with top biopharmaceutical companies to bring new products to market.  Nektar’s pipeline of late stage molecules include Amaikacin, Ciprofloxacin, Fovista, BAX 858, and NKTR-102.  Amaikacin Inhale is delivered directly to lungs to treat gram-negative ventricular pneumonia.  NKTR-102 is first PEGylated small molecule, first in its class, to treat breast cancer.  It has passed safety and efficacy markers and is showing to significantly improve overall survival and endpoints will be announced next year.  Nektar is also getting positive results from some of its early stage molecules.  Recently Nektar presented positive preclinical data for NKTR-214 for immunotherapy treatment.  Nektar is developing pain management portfolio and recently got fast track designation for NKTR-181, a new oral opioid analgesic molecule for the treatment of moderate to severe chronic pain.  NKTR has filed for regulatory approval in EU for MOVENTIG, comprising of once only daily oral tablet, to treat opioid induced constipation.  Hora concluded saying that Nektar has very robust pipeline of highly promising molecules.

English: Example transdermal patches. On left is a ‘reservoir’ type, on the right a ‘matrix’ version. Both contain exactly the same level of the same active ingredient. (Photo credit: Wikipedia)

Dr. Zander Strange, VP of Bus Dev. and Corp. Dev. at Zosano Pharma shared about their products based on novel transdermal delivery technology.  Zosano’s rapid onset system allows drug delivery to occur, almost painlessly.  The drug is delivered close to the capillary bed, allowing it to quickly dissolve.  The short-wear-time patch consists of microneedles coated with Zosano’s proprietary formulation of an existing drug, attached to an adhesive patch.  Therapeutic effect is expected to occur within 30 minutes or less, in an easy, pain free administration.  Zosano products are in dry formulation, thus vastly improving product stability and long shelf life, in addition to allowing for easy travel and storage at room temperature.

CBA annual conference was packed with impressive lineup of speakers, interspersed with plenty of networking opportunities.  For additional information, please go to www.cbasf.org .      

PS – EPPIC Digital Health event http://bit.ly/1uwQ6af is today at 6 pm in Palo Alto. Please register ASAP at http://www.eppicglobal.org .

“Entrepreneurs must Focus on Market Pain” – Norman Winarsky, SRI

EPPIC organization was found in 1998, with a mission to promote networking, entrepreneurship, and mentoring for life science professionals.  Each year, EPPIC Annual Conference provides a wonderful forum to realize this mission. EPPICon on March 29, 2014 was held at Westin, SF and began with opening remarks by Dr. Norman Winarksy, Vice President at SRI Ventures.

SRI or Stanford Research Institute was found in 1946 to help Stanford University professors make an impact in the world.  It has a staff of 2500, of whom 1000 have advanced degrees and current revenue is in the range of $600M. Many revolutionary technologies like the mouse (invented by Doug Engelbart whom I had an opportunity to meet, before he passed away, when I took his picture inserted here with the first red mouse that investor Peter Gerber is holding), electronic banking, robotic surgery (which spun out as Intuitive Surgical), and SIRI to name a few, have come out of SRI.  All SRI personnel are taught to identify the value proposition and work towards that goal, said Winarksy. SRI is a non-profit organization but gives 34% of royalty to the individual or the team that worked on the specific technology and that is how SRI competes with high salaries in Silicon Valley.  SRI process always begins with identifying the market pain, ideally a larger market opportunity.  Out of about 2000 opportunities identified, about 3-4 get funded and get about 10X return; many of the others become licensing deals and the rest die.  Currently Tempo, a smart calendar is showing a lot of promise, said Winarsky. This was a great start to a day that proceeded with excellent panels, speed pitch sessions and SIG networking opportunities.

Next EPPIC event will be held on May 6 at 6pm at Cubberley Theater, 4000 Middlefield Rd, Palo Alto.  Dr. Sarvajna Dwivedi, CSO at Pearl Therapeutics will talk about the entrepreneurship journey that took him and his co-founder to build from a tiny spin out, from Nektar Therapeutics, a world class multi-site organization.  Pearl Therapeutics was bought by Astra Zeneca last year, for $1.15 B.  To register for the event go to http://www.eppicglobal.org .

On “Building a Pearl” – Story of Pearl Therapeutics from Concept to Acquisition by Astra Zeneca for $1.15B

Pearl Therapeutics is a huge success story in the biotech world.  At www.bio2devicegroup.org event, Dr. Sarvajna Dwivedi, co-founder of Pearl Therapeutics talked about his own professional journey and about Pearl team, technology and products, that brought the company to pearly stunning $1.15 Billion exit.  Pearl Therapeutics was acquired by Astra Zeneca in June, 2013.

Dwivedi began the talk by paying tribute to his mentors, his father, Professor Rewa Prasad Dwivedi, his first role model and a reknowed Sanskrit scholar and poet, his professor Dr. Alan Mitchell  at University of British Columbia who imparted important lessons on staying true to fundamentals and understanding the properties of nature, and Silicon Valley’s prolific inventor Mr. Mir Imran, who told him long before he needed to raise money, “don’t ever take investor’s money, unless you can treat it as your own”.  Dwivedi said he carried all those valuable lessons in his professional journey.

After his education where he worked on tablets, Dwivedi was invited to join Glaxo to work on inhalation products.  When he was concerned about making a jump from tablets to inhalation products, he was told “you know how to keep particles together, you would know how to keep them apart too”.  From Glaxo, he went on to Dura, where he worked on an electromechanical inhaler system, a complex 50 part device.  Then at Alkermes, Dwivedi put together a team which designed a device with a precessing capsule inside.  Each of these opportunities contributed to giving him a stronger grounding into fundamentals.

Eventually, his career journey brought him to Nektar Therapeutics.  Nektar was focusing on systemic conditions like diabetes, to be treated by inhalation delivery of drugs like insulin, and on anti-infective therapies for lungs.  Dwivedi and his colleagues were looking at delivering drugs uniformly into the lungs for diseases such as asthma and COPD, and especially make drug combinations with standard metered dose inhalers.  Global COPD or chronic obstructive pulmonary disease and asthma market is projected to reach $47 billion, by 2017.  These were compelling clinical problems that Dwivedi and his colleagues were trying to solve, but Nektar chose to stay focused on other opportunities.  Eventually, Dwivedi and his co-founder Adrian Smith formed Pearl Therapeutics and spun it out as a separate company.

Image via CrunchBase

Pearl Therapeutics has combined two bronchodilator drugs in one inhaler, and put it into Phase III.  Pearl has now demonstrated that it can also combine three drugs, to treat the fatal lung condition, COPD.  These drugs typically do not mix well together in a common inhaler and that leads to less than ideal distribution of the drugs in the lungs.  Pearl’s secret is its proprietary technology.  Dwivedi said the lessons he learned earlier in life regarding staying true to fundamentals and to not fight nature, were most useful in navigating these challenges.  The nature of particles is to coalesce, and therefore it’s very difficult to keep them separate for aerosolization purposes.  This can be achieved easily with liquid propellant suspensions, such as those in commonly used metered dose inhalers.  Pearl creates these suspensions with a proprietary technology utilizing specially engineered phospholipid porous particles.  When these inhalers are actuated then the porous particles go back from liquid to vapor, facilitating consistent and uniform inhalation delivery. The porous particles traverse the back of the throat easily and spread aerosols throughout the lung.  Astra Zeneca saw the tremendous promise in this technology, the product progression achieved by Pearl, the value of the product pipeline at Pearl, and the Pearl team assembled by Dwivedi and his co-founder, Smith.  AZ forked over $1 B+ and acquired Pearl, with a promise to enable Pearl to continue to operate independently.  This was very interesting talk and generated a great deal of discussion.