A Braver Agenda - Reflections On The BIO Investor Forum 2014
By Wayne Koberstein, Executive Editor, Life Science Leader
Follow Me On Twitter @WayneKoberstein
Fourteen pages of tweets. Many retweets, favorites, and conversations. Plus a sheaf of business cards, reams of notes, and memorable moments. All accumulated in only two days at the BIO Investor Forum, October 7 and 8, in San Francisco.
From the moment I sat down with early coffee on the first day, the networking began. People introduced themselves, most told me their story, but many also took the time to make a personal observation about our surroundings, the beautiful day outside, the news… As almost everywhere else, the subject of Ebola frequently surfaced. Was it just on our minds because it was threatening “our people” for the first time? Yes. But more on Ebola later.
Here is the kind of thing that can only happen at a conference. You meet a stranger, who turns out to be the CEO of a Wisconsin company, InvivoSciences, producing a “3D” tissue-assay technology for more life-like models in compound profiling and patient segmentation. Have they heard of the Critical Path Institute? “It is a major doorway to precompetitive industry collaboration aimed at improving drug development,” you say. The CEO looks enlightened and makes a note. Where could it lead? Not just another tweet or Facebook entry, but to more human interaction and validation extending from the personal, early morning exchange.
At the same time, the cyber world has merged well with the living world of conferencing. Tweeting to a hashtag group, in this case #BIF14, attendees and remote observers create a temporary community around the event. There is more camaraderie than competition in the Twitter dimension, though a few of us — such as Luke Timmerman, now writing a book while away from his usual industry publication — are especially ardent tweeters. For me, tweeting has now replaced a lot of furious note-taking on my long-time friend, the yellow legal pad. I can reconstruct my experience of the event from the hashtag tweets.
BLENDED SESSIONS
Last year at BIF, I was just beginning the Combination Cancer Immunotherapy Roundtable project and focused almost entirely on companies in the cancer area. (See the first three parts of the series in the September, October, and November issues of Life Science Leader.) That was easy, because cancer, and cancer immunotherapy, dominated last year’s conference. This year, I sought and encountered the greater proportion of non-cancer companies presenting.
Coincidentally, considering the breakfast talk with InvivoSciences, my choice for the first session, Sparrow Pharmaceuticals, cited patient-response data from other companies’ clinical trials to show how its own development candidate may have the right pharmacologic properties to treat nonalcoholic fatty liver disease (NAFLD), as well as the more serious, comorbid condition of nonalcoholic steatohepatitis (NASH) and Type 2 diabetes. The trials were of similar “HSD-1 inhibitor” compounds in the pipelines of Roche, Abbott, and Pfizer supporting proof-of–concept for their MOA — an interesting new approach to hepatitis and diabetes: reducing fat in the liver.
My next visit to a presentation, by ORIG3N, was not because it is pronounced the same as my home state. The company produces induced pluripotent stem (iPs) cells from patient blood, skin, or hair cells for personalized diagnosis that guides treatment of rare genetic diseases of the heart, liver, and nervous system. Its technology creates patient-specific regimens through drug efficacy screening in engineered disease models using each patient’s iPs cells.
After a stop at Heat Biologics, which will soon be featured in our combination cancer immunotherapy roundtable, I skipped out of a hot “fireside chat” with J&J’s head of innovation to see a tiny company, Humanetics, which is developing a radioprotective agent, BIO 300, with funds from BARDA and the NIH, seeking indications in radiation over-exposure and related conditions such as radiation-caused lung cancer, pneumonitis, and fibrosis. I found the drug interesting for its multiple MOAs — targeting inflammatory and antioxidant pathways, inhibiting tyrosine kinases, and modulating pathways that control cell-cycle division.
PaxVax was next: a company creating vaccines for the most dangerous, and most ignored, worldwide diseases. At least they have been ignored, until now with the veritable Ebola freakout. (Suddenly, vaccines are everyone’s hope — except for the awkward fact that no one wants to pay for them.) PaxVax particularly defies the industry’s current vaccine model by aiming for “quick, cheap, and socially responsible” vaccines for the world’s worst diseases. Fortunately, an oft-maligned taxpayer-supported group, the FDA, has granted the company a Priority Review Voucher reserved for new treatments of neglected tropical diseases. No idealistic fool, however, the company is pragmatically targeting travelers from affluent to poor countries as its first market. PaxVax is also jump-starting its business with product acquisitions rather than its own discovery, and aiming for single-dose vaccine forms to cut delivery costs.
With Theravectys, I tweeted that it was good to hear from another Paris-based company besides Sanofi. This vaccine company has its roots in the Sanofi-acquired Pasteur Institute, however — and by extension, back to Louis Pasteur himself. Theravectys says its novel vaccine vectors are engineered for intense, long-lasting response and safety, compared to conventional vaccine technology. During its presentation, I am struck by this thought: Will vaccines and immunotherapies help reboot the life science industry's reputation for miracles? If people still hold that image of the industry in their minds, we can largely credit vaccines for putting it there.
HOLDING OUT VALUE
It is worth noting that Theravectys is planning a U.S. IPO. Despite the siren call of inversion calling the industry to other shores, it appears the USA is still the place to go if you want to be in the game. Also, like many small companies, Theravectys is looking for an early stage partnering deal.
Despite the persistence of early partnering, I did notice a counter-trend at this event — small companies are growing more aware of their own market caps, as are their potential partners in Big Pharma, possibly slowing the pace of deal-making as one side pitches its value while the other hunts for bargains. And I heard more companies say they are resisting early, or even late, partnerships with large pharmas altogether, preferring to take their products all the way through development to approval, and possibly into the commercial realm. Independence may be a strong motivation for many companies in the current IPO boom.
“Going public has allowed us to go unpartnered longer,” said Robert Ward, CEO of Radius Health, at a session on the JOBS Act and IPOs. This theme of escaping onerous structured deals with their staggered, milestone-based payments resounded frequently throughout the Forum. The problem is drug-development costs. Oncomed Pharmaceuticals CEO Paul Hastings pointed out that many Phase 2 trials are now almost as large as typical Phase 3 trials once were, preserving the need for the development skills of large-pharma partners. A small company may also be unprepared for public status and the related demands for communication with the outside world.
Stop for an editorial aside. The IPO session ended in my amazement at the answer to a question I posed to the panel: Did the JOBS Act have a noticeable effect on the number or value of life science IPOs? “No,” was the answer, either endorsed or unchallenged by the panelists. I looked around to see others in the audience joining me in astonishment, but the session then closed, and so did the discussion.
AREA SPOTLIGHTS
A litter of companies in neurology made that area one of the more active ones at the Forum. Like others, Newron Pharmaceuticals targets Parkinson’s Disease (PD); in its case, with safinamide, a Phase 3-completed drug to lower patients’ need for l-dopamine therapy — a quite significant goal that anyone who has experience with the disease can testify. Newron also has agents for ALS and Rett’s syndrome in Phase 1-2 as well as earlier candidates for schizophrenia, severe PD, and others in the CNS space.
Two additional neurology companies I surveyed, in brief: CoLucid Pharmaceuticals has completed a Phase 2b trial with lasmiditan, first in a new “neurally active” class with a novel MOA for migraine, possibly challenging the older vasoconstrictors and triptans without their side effects. MentiNova, with funding from the Michael J. Fox Foundation and the Foundation Venture Capital Group, has completed preclinical development of a reformulated painkiller for L-Dopa Induced Dyskinesia in PD.
Some mechanisms span a number of disease areas. Some neurodegenerative conditions — muscular sclerosis (MS), for example — can also be seen as autoimmune diseases. One of the drugs in the pipeline of Sevion Therapeutics stems from research prompted by MS patients who went into remission after being stung by a scorpion. One of the products of Sevion’s “novel cow-antibody” platform is a scorpion venom-like antibody that modulates effector memory T cells involved in MS as well as arthritis, psoriasis, irritable bowel disease (IBD), and graft-versus-host disease (GVHD). Sevion has its own drug discovery and development pipeline in house and a partnership with BMS for it’s cow-antibody platform and “membrane protein” scaffolds.
Other areas with multiple companies presenting included cardiovascular, gastrointestinal, and of course, cancer. I have written about the early stage company BEAT Bio in Life Science Leader’s November Companies to Watch, but I also visited Juventas Therapeutics, which is further ahead with its heart-failure candidate, JVS-100, a non-viral plasmid that encodes for stromal cell-derived factor-1 (SDF-1). Now in Phase 2 trials for symptomatic ischemic HF and critical limb ischemia, JVS-100 uses a tissue-healing MOA to treat those conditions. Juventas uses a DNA-plasmid technology to produce an off-the-shelf drug as an alternative to stem-cell therapy for tissue healing.
In the GI area, Relypsa is developing non-absorbed polymeric drugs, with one, patiromer FOS (for oral suspension), in Phase 3 for hyperkalemia — or excess potassium in the blood. The risk of hyperkalemia is high in chronic kidney disease, where it forces the discontinuation of RAASi (renin-angiotensin-aldosterone system inhibition) medications. It is also a GI condition because the colon is responsible for eliminating potassium from the kidneys, and the Relypsa drug stays in the colon to stimulate that action.
Idiopathic ​Gastroparesis sufferers, and particulary diabetes patients with GP, are the first target of ETX Pharma, which has in-licensed several Phase-2 GI assets. One of its candidates is a potential rival to the current top drug in Crohn's disease and ulcerative colitis, Humira.
Cancer had many entries, of course — most all of them claiming some connection to immunotherapy this year. Few of the leading companies developing checkpoint inhibitors or vaccines were present, however, although CAR-T and other patient cell-based therapies presented, leading me to acknowledge their eventual adoption where off-the-shelf treatments fail, despite serious questions about their cost and logistics. MOAs were all over the board. A couple of examples:
OncoSynergy uses “SMART” targeting against solid cancers, saying it is inhibiting parallel pathways not hit by Avastin — “combination therapy in one.” Immungene attaches immune effector molecules to antibodies targeting tumors. The company is looking at attaching checkpoint inhibitors to its antibodies — another combination therapy in a single drug. Immunegene says preclinical testing with local administration of its first immune effector-antibody agent shows a strong effect, but the company faces a long path ahead in development.
PLENARIES IN PLENTY
During its two-day span, the BIF also presented several plenary sessions and a variety of “therapeutic workshops” and other general-interest gatherings. Besides the aforementioned JOBS Act/IPO discussion and the visit by Ken Drazan of J&J, there were sessions on alternative funding solutions, industry/foundation partnerships, biotech forecasts, the FDA’s breakthrough designation, reimbursement challenges, T cell therapies for cancer, electroceuticals, and gene therapy — plus another “fireside chat,” with the CEO of bluebird bio, Nick Leschly.
Then there was the session on Ebola, which fortunately did not represent the otherwise excellent programming at the Forum this year. The best thing I can say about it is the standing-room-only turnout showed the intense interest in the topic at the event. From conversations with many fellow attendees, I believe the interest is genuinely humane and, of course, full of hope in the potential medical solutions to Ebola and other terrible contagions. But the Ebola session was hampered by an unusually strict format and limited content. Journalists were not allowed to ask questions of the single guest in “A Conversation with Tekmira’s President and CEO, Mark Murray.”
It might have been livelier if we had. Most people I spoke with about the session thought Murray had spent a bit too much time on his company’s background and not enough on the crisis. Tekmira is on fast-track development with TKM-Ebola, an anti-Ebola viral RNAi therapeutic in a lypholized form for non-cold storage, key to delivery in non-developed regions. (The “vaccine” is now on partial clinical hold by the FDA to clarify its therapeutic pathway.) The company has done extensive work with colleagues in West Africa, and Murray referred to their interesting anecdotes from the front lines of the epidemic, but he gave no real details. The audience seemed generally disappointed.
In my view, the BIF was brave to hold an Ebola session — any Ebola session. Industry conferences of the past rarely addressed such a “third-world” crisis, especially in a plenary session. We need more discussions and alliances among industry, government groups, and NGOs to evolve practical solutions for this inevitably traveling virus. Industry needs to think BIG about Ebola — not just about products or their commercial value. Industry companies have tentacles of relationships threading into the areas where such diseases emerge. Wherever possible and needed, the industry should use the total knowledge it derives from those connections to help lead development of the healthcare infrastructure.
At the end of the Forum, on my way out to catch the train to the airport, I met the CEO of the German company Protagen, Stefan Müllner, and we spent the ride together in conversation. Protagen is a “novel diagnostics” company, using its SeroTag autoantibody profiling system to identify diagnosis and drug targets in more than 100 autoimmune diseases. The system can be used for patient stratification in clinical trials, which has helped more than a few drugs avoid failure and achieve success in gaining approvals. Müllner said SeroTag may also be used to predict the performance of expensive approved drugs, such as Humira, in individual patients, thus saving the costs of inappropriate prescribing.
It occurred to me Protagen’s technology could address a lot of issues hashed over at the BIF this year — from drug mechanisms to payer perspectives. It was also the second year I’ve shared a train ride with an attendee learning about them and their companies. I am naturally left wondering: who will it be on this train with me next year? Or for that matter, on the rides to or from our Outsourced Pharma West event, November 10 and 11, in San Francisco. Maybe I will see you there!