Novel Approaches to Drug Development – 2015 Eppic Annual Conference

Drug development panel discussed how the technological advancements in Big Data, Machine Learning and Cloud Computing, when paired with focus on combination therapies that include for instance, anti cancer and immuno oncology agents, or paired with next gen sequencing technologies, and advanced companion diagnostics, with relentless focus on patient outcomes, may open new frontiers in cost effective drug development.

Drug development panel was moderated by Dr. Suneel Gupta, Chief Scientific Officer at Impax Pharmaceuticals.  Gupta has over 25 years experience in pharmaceutical R&D, specifically around drug delivery technologies.  Gupta shared the story of how Impax launched RYTARY, an extended-release oral capsule formulation drug, for the treatment of Parkinson’s disease, and took it in a span of 3.5 years, with $100M, from benchmark to launch.  This is Impax’s first branded drug internally developed and approved for commercialization and it was achieved with “relentless execution”, said Gupta.  Gupta’s advice to the entrepreneurs was to focus on the patient, not technology; to focus on what the product does, not what the product is made of.  He also advised to keep the the focus on the effect and go for big effect size, to get the drug approved faster.

Brandon Allgood, CTO at Numerate began by talking about the challenges of existing computational methods which so far have been strictly dependent on either high resolution crystal structure data or very clean SAR screening data (QSAR).  These models did not work well where computing is most needed, with disparate data, with emerging targets, and in high content, low throughput biology, and for multi target optimizations, said Allgood.  However, with a vast number of technological advancements in cloud computing, big data, and machine learning algorithms, Numerate has overcome major challenges in drug discovery, said Allgood.

Numerate has created a powerful drug design platform that can rapidly deliver novel leads on targets, without the need for a crystal structure and with very limited SAR data.  It can be used with just some ligand data and that is perfect for emerging targets, said Allgood.  Numerate’s machine learning algorithms can integrate and make predictions from small amounts of public data available from patents, literature review etc. and make accurate predictions and give google or netflix type ranking to data design.  It can handle noise and bias and give tolerance windows to address inter lab measurement variance.  Numerate has built 2100 off target models and also has advanced ADME models, said Allgood.  Speaking of some of the challenges in this area, Allgood said, public data is noisy and biased, while private data is private.  He suggested following changes.  1) To spur innovation, big pharma should be encouraged to release data so others can apply machine learning algorithms to more data.  2) There is a need to put in place some standards for machine learning to standardize lab validations.  3) While genomics has received a bulk of funding, there is need to put investment behind research on small molecule drugs; “they still have a future”, said Allgood.

Dirk Brockstedt, SVP of R&D at Aduro BioTech, began by saying 2013 brought in a new era in cancer immunotherapy with approvals for Yervoy, Provenge, Opdivo, and Keytruda.  The opportunity exists for rethinking about the biology and cancer treatment and look for combination of anti cancer and immuno oncology agents that can move the cure to the right for an increasing proportion of cancers, said Brockstedt.  The key is to target the immune and not the cancer cell in developing innovative therapies.  We need to also develop new clinical endpoints, develop new trial designs with new statistical methods, and consider novel regulatory paths for accelerated approvals of combination therapies.  When only a subset of patients respond well, we need to apply novel technologies and methods for patient identification and stratification, said Brockstedt.

Brockstedt talked about Aduro Biotech’s novel approach for tackling the disease, with listeria bacteria.  Here is my previous blog on Aduro’s approach http://bit.ly/JqDJ3K  and here’s link to recently aired Scott Pelly’s segment on 60 minutes, on the use of polio bacteria for treatment of glioblastoma http://tinyurl.com/pkspcmz . These potential therapies are in early stage and it remains to be seen how successful the genetic engineering will be to render them useful as cancer drugs.

Eric Peters, Group Leader of Companion Diagnostics at Genentech discussed the challenge of expediting drug discovery and development through the use of next gen sequencing technology.  Currently the cost to bring a new drug to patients (including failures) is around $2.6 B.  There is only 12% success rate in drug development.  However, also the knowledge of disease heterogeneity is rapidly evolving.  Now we speak not of lung cancer but lung cancers, said Peters.  There is a need for large scale biomarker and phenotype datasets.  Access to high quality data from multiple sources is the most essential element.  Patients’ access to complete range of testing and comprehensive diagnostics will play a big role in the future, and will become a standard of care in the future, said Peters.

Here are some additional blog links for your convenience
EPPICon 2015 keynote by Vivek Wadhwa – http://bit.ly/1abPwr5
“EPPICon 2015 Digital Health Panel Preview” http://bit.ly/1EQtd5y
“EPPICon 2015 Keynote by Kim Bush on “Tackling Global Health at Gates Foundation” http://bit.ly/18SV1cx
Feel free to browse my blog for past EPPIC conferences and other articles.

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 .