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 .

Regenerative Medicine and Aesthetic Applications

Gail Naughton, Chairman and CEO of Histogen talked about regenerative medicine at www.bio2devicegroup.org event.

Naughton began by sharing the history of regenerative medicine.  So what is regenerative medicine?  It is the process of replacing or regenerating human cells, tissues or organs to restore or establish normal function and it holds promise for regenerating damaged tissues and organs.  It was an exciting discovery earlier that if you grow cells in a 3D environment, instead of a plastic cup then they become tissues and form functional epidermis, said Naughton.  This would require tremendous cross-functional effort between bio-engineers and surgeons.

Earlier technology was based on allogenic fibroblasts obtained from neonatal foreskins, from routine circumcisions.  The focus was on wound healing because of fewer complications due to topical applications.  The stem cell technology responded to wound environment and secreted numerous growth factors.  One of the first companies in this space was TransCyte that focused first on facial burns and then on diabetic foot ulcers.  It showed excellent and persistent wound healing and was very exciting.  However, cool technology does not translate into reimbursement.  At the time, wound healing was a low paid proposition.  Ischemic wounds occur as a result of blocked blood flow to medium and small vascular beds in the body.  It was found that stem cells cure ischemia and restore blood vessels.  Between 1996 and 2000, there were various companies targeting ischemic wound healing, including Integra, TransCyte, Apligraf, and Dermagraft.  There was a lot of hype but still not much success in getting reimbursement.  Additionally, these products had low shelf life and required to be stored in freezers.  It took several years before the realization that cost of amputations and other procedures far outweighed the cost of these technologies.

During that time, Advanced Tissue Sciences licensed NouriCel product line to SkinMedica for skin care applications.  Then Inamed licensed rights for human collagen product applications from Advanced Tissue Sciences.  The company was later bought by Allergan for $375 million.  Increased collagen secretion, even when topically applied, had positive effect on decreasing anti oxidants.  One of the lessons learned was, that the path to generating revenues was through cosmetic and aesthetic applications.  Skin care was an exploding market and consumers were willing to pay.

Allogenic stem cell technology, particularly from neonatal foreskins was making way for many skincare options.  Next to come was autologus stem cell technology with cells derived from person’s own blood, to reduce major complications due to body’s immune response.  Recombinant proteins derived from the expression of recombinant DNA within living cells, offered further options.  Cytori Therapeutics Celution System had a proprietary centrifuge device that enabled access to adult adipose-derived stem and regenerative cells (often from liposuction and other procedures) for later cosmetic use.  Cytori technology automated and standardized the extraction, washing, and concentration of the patient’s ADRCs for present and future clinical use.

Australia based Avita offered point of care cell treatment with great application for burns.  Avita’s ReCell Spray-on Skin is a rapid, autologous cell harvesting, processing, and deliver technology that allows surgeons to treat burns and other skin problems using patient’s own cells.  This real time technology accelerates healing, minimizes scar formations, eliminates tissue rejection, and reintroduces pigmentation to the skin.  Again it becomes apparent that revenue generation is easier for aesthetic applications.   Fibrocell Science is another exciting company with autologus fibroblast technology.  Fibroblast cells that are responsible for production of collagen, a protein that gives the skin its strength and elasticity and extracellular matrix proteins, are most common cells of connective tissue.  Autologous fibroblast cells derived from individual’s body are used for variety of aesthetic applications.  Regardless of the fact that people may or may not need autologous technology for wrinkle removal, the marketing is working, said Naughton.  People are happy to get a jar or “customized” skin cream for almost $500.

Naughton’s company Histogen is also currently focusing on aesthetic applications, particularly on skin and hair growth.  Conditions that make the embryonic environment special was a moment of major insight and excitement, said Naughton.  Histogen has proprietary technology that mimics the low oxygen, low gravity embryonic environment.  These hypoxic human dermal fibroblasts HDFs are derived from similar embryonic conditions that lead to production of vital proteins and growth factors.  From this process, Histogen extracts two products, a soluble human cell conditioned media (CCM) and an insoluble human extracellular matrix (hECM).  With one technology, two formulations, Histogen sees ahead a variety of applications to address a broad range of markets, said Naughton.  Before and after pictures of wrinkles and hair growth showed clearly the impact of Histogen technology and raised tremendous excitement among the attendants.  Histogen raised $10M in Series A round and is currently raising Series B, to support upcoming clinical trials and scaled up manufacturing.

Tissue Engineering and Regenerative Medicine International Society (Photo credit: Wikipedia)