By Wayne Koberstein, Executive Editor, Life Science Leader magazine
Follow Me On Twitter @WayneKoberstein
There is no grand plan for a whole year of Companies to Watch (CtW). Each month, a single candidate makes the cut for a single column. Nevertheless, patterns emerge among the CtWs as the year progresses and come into focus as it ends. Perhaps I make them half consciously. Every year so far, I have made a wide selection of possible CtW candidates according to the simple criteria — small company, developing new therapies, little press coverage, interesting and instructive story. A CtW might come from the larger group of my meetings and interviews or out of the constantly churning pool of startups and upstarts in this wondrous industry. As I write this, I have just scheduled more than a dozen meetings during the week of the 2017 J.P. Morgan Healthcare conference, selected from more than 300 PR pitches, and am preparing for a trip in February and more interviews at the BIO CEO and Investor event. Many of those conversations will form the basis of CtWs, but many will also contribute to other series, features, columns, or blogs produced during the year.
This year, some clear patterns showed themselves in the 10 CtW columns we published in 2016. First, the featured companies range fairly evenly from just-off-the-bench early to regulatory-submission late. It is safe to say that every company reflects the characteristic risks that come at each stage along the development path. At the earliest points, hopes are high, success or failure lies far in the future, and merely communicating and “proving” your concept is the immediate challenge. Further along, though, as you approach testing in humans, the pressure rises; get the trial design wrong, and you may have sown the seeds of your own defeat. And with each new phase, the ante jumps higher — you must raise and spend more money, hire more people, batten down your IP, and work through the racket raised about your product by the usual crowd of hypesters and doubters.
The 2016 CtWs report making progress at their stage — all, that is, except one, felled by safety issues, otherwise known as the vagaries of the human body in reacting to new therapeutic agents. Not as random as roulette, but often as unpredictable. In truth, our exception is closer to the rule than the rest of our CTWs, seen in mid-development, and still working toward their end goal. In the following, we let the companies update their stories as we continue to watch them in 2017.
At the FDA’s door this year with Phase 3 data and a planned NDA for a licensed drug developed as the first treatment for a rare neuromuscular disease — and maybe others.
"In 2016, Catalyst continued to focus on bringing Firdapse [amifampridine phosphate] to patients with Lambert- Eaton myasthenic syndrome (LEMS) and other neuromuscular disorders through the FDA approval process. In December 2016, Catalyst launched a confirmatory Phase 3 clinical trial of Firdapse in patients with LEMS. This Phase 3 trial, which received a Special Protocol Assessment (SPA) from the FDA, will support Firdapse’s new drug application (NDA) to the FDA. Catalyst expects data from this trial and its NDA submission in the second half of 2017.
Catalyst also has continued to evaluate Firdapse in patients with congenital myasthenic syndromes (CMS) and MuSK-antibody positive myasthenia gravis (MuSKMG), with clinical trials running for both indications. In December 2016, the company expanded its CMS clinical study to include adults with CMS, in addition to pediatric patients with certain genetic mutations of CMS. Data is expected later in 2017. In 2016, Catalyst also proudly published case reports of clinical efficacy of its GABA-AT inhibitor, CPP-115, in patients with infantile spasms.
Catalyst will have multiple clinical milestones in 2017, including data from its second Phase 3 trial of Firdapse and data from studies of Firdapse in CMS and MuSK-MG. The company expects to submit the NDA to the FDA for approval of Firdapse in patients with LEMS later in 2017 as well. The FDA approval will allow, for the first time, all patients with LEMS to have access to the only effective treatment for this debilitating disease."
Completing midstage trials for its two lead bioconjugate drugs in critical limb ischemia and osteoarthritis, and preparing for some serious money raising.
"Symic Bio has experienced rapid growth since February 2016, nearly doubling in size. We’ve relocated (to Emeryville, still in the Bay Area) to expand our office and lab space. Our trial for osteoarthritis of the knee, initiated in June, completed enrollment in November. Our program for vascular interventions in critical limb ischemia continues to progress. This allows us to look forward to two efficacy readouts in 2017: results from SB-061 in osteoarthritis in the second quarter, and results from SB-030 in vascular interventions in the second half of the year. SB-061 is designed for both disease modification and pain management in osteoarthritis, while SB-030 is designed to block inflammation following cardiovascular procedures to prevent serious complications. Demonstrating efficacy in either trial will validate the potential of our library of compounds as a new therapeutic class in humans for the first time and hopefully draw attention to the distinct possibilities of therapeutic approaches based on matrix biology. We continue to explore applications for our platform in oncology, fibrosis, and CNS disorders. In addition, we expect to complete a significant Series B financing early in 2017. If conditions permit, we may move toward an IPO in 2017 as well."
Progress by an upstart startup in taking on the world of abuse-deterrent pain treatment as opioids of all kinds come under increasing fire.
"2016 was a momentous year for Egalet. In August, the company went through its first FDA advisory committee for Arymo ER (morphine sulfate), where the committees recommended approval of Arymo and voted that, if approved, it should be labeled as an abuse-deterrent product by the intravenous, nasal, and oral routes of abuse. Leading up to the potential approval of Arymo, the company has experienced a period of growth in the United States, including the addition of 16 new employees in 2016, bringing the total employees in the United States to 62 (88 globally), with plans to add another 75 employees in just the first quarter of 2017. The company also submitted an sNDA (supplemental new drug application) to the FDA in December for Oxaydo (oxycodone HCl, USP) tablets C-II, to support an abuse-deterrent label claim for the intravenous route of abuse, and received pharmaceutical composition patent protection for Oxaydo through 2024. As the company looks into 2017, the first half of the year will be focused on launching Arymo ER, once approved."
Completing and launching Phase 2b trials for a “microbiome modulator” to treat and prevent vaginosis, urinary tract infections, and infertility, while aiming longer term at HIV and GI.
"Osel continued to advance clinical development of its lead product, Lactin-V (Lactobacillus crispatus, CTV-05) in 2016 with two Phase 2b clinical trials. An NIH-sponsored study to investigate Lactin-V for treatment/prevention of recurrent bacterial vaginosis was initiated at four U.S. sites in 2016. In addition, an ongoing Lactin-V study for treatment/prevention of recurrent urinary tract infections continues at the University of Washington. Both of these indications are major unmet medical needs associated with dysbiosis of the vaginal microbiome, characterized by a diverse microbiota low in protective Lactobacillus. Lactin-V is a microbiome modulator that restores vaginal Lactobacillus. A third Lactin-V study is scheduled to begin in 2017 in Europe to improve the success rate of in vitro fertilization (IVF) for infertile women with abnormal vaginal microbiota (AVM). AVM has been shown to significantly reduce the clinical pregnancy rate of IVF patients.
Osel’s genetically engineered Lactobacillus product, MucoCept-CVN, is advancing toward the clinic. A pre-IND meeting was held with the FDA in 2016 and an IND will be submitted in 2017. MucoCept-CVN contains a vaginal strain of Lactobacillus jensenii that secretes a potent HIV inhibitor, cyanovirin-N. The product is being developed in conjunction with UCSF (University of California at San Francisco) and the NIH to prevent HIV infection in women.
Osel is also developing a GI microbiome product, CBM588 (Clostridium butyricum Miyairi 588). Collaborations are ongoing to test a new high-potency formulation of CBM588 in HIV-associated diarrhea and graft-versus-host disease. CBM588 is known to have antidiarrheal and immunomodulatory activity."
Prepared to launch a Phase 2 program with its lead drug candidate for levodopa-induced dyskinesia and various forms of spasticity with a stronger, experienced team.
"Progress made since May 2016:
Lead program, dipraglurant for levodopa-induced dyskinesia associated with Parkinson’s disease (PD-LID): POC (proof of concept) data published in peer-reviewed journal, Movement Disorders; and significant progress made in the preparation to start registration trials, including interactions with regulators and completion of registration trial designs. Preparation of a Phase 2 POC clinical trial with dipraglurant in focal cervical dystonia was also completed. Our second clinical-stage asset’s (ADX71441) preclinical profile was published in a peer-reviewed journal, Neuropharmacology; our NIDA (National Institute on Drug Abuse) collaboration generated spectacular data in a nonhuman primate model of cocaine-seeking behavior; and preclinical data in a model of spasticity was also generated. Our discovery programs also made significant progress with a new collaboration with NIDA, under which NIDA will test ADX88178 in models of cocaine addiction. At the corporate level, we increased equity research coverage, with David Sherman of LifeSci Capital and Marcel Wijma of Van Leeuwenhoeck Institute picking up coverage. In addition, we strengthened the team with the hiring of Roger Mills as chief medical officer. Dr. Mills is the ex-CMO of Acadia and credited with the development of pimavanserin for Parkinson’s Disease Psychosis.
Plans for 2017:
We plan to secure resources through collaborative arrangements or capital raising to execute our strategy to develop dipraglurant in PD-LID and dystonia and ADX71441 in addiction and Charcot-Marie-Toothtype 1A neuropathy. We also plan to continue to advance our preclinical programs through collaborative arrangements with patient advocacy groups, governmental organizations, and academic institutions."
Now an example of how many, really most, drug development programs end early.
"Tunitas is in the process of winding down due to some safety issues in the recent Phase 1 clinical trial for its lead candidate Epsi-gam, a genetically engineered bifunctional human fusion protein for allergic reactions."
Continuing a move from supplier with novel oral-formulations to developer of a pipeline of urinary and gynecological drugs in mid-stage clinical trials.
"Since being featured in Companies to Watch, Enteris BioPharma has completed dosing patients in our Phase 1 study of Tobrate, an oral tablet formulation of tobramycin for the treatment of uncomplicated urinary tract infections (uUTIs). The initiation of the Tobrate clinical program was a significant event for Enteris as it provides the company with an opportunity to advance a potentially high-value and highly differentiated therapeutic for the treatment of uUTI, a condition that affects approximately 10 million U.S. women each year. Tobrate is an expansion of Enteris’ internal drug pipeline, which includes Ovarest, a Phase 2a-ready oral peptide for endometriosis. In 2017, Enteris expects to announce data from the Tobrate Phase 1 study and plans to initiate a Phase 2a study of Ovarest in the first half of 2017. Additionally, Enteris anticipates securing two or more license agreements involving the company’s proprietary Peptelligence platform, a novel formulation technology that enables oral delivery of molecules that are typically injected, including peptides and BCS class II, III, and IV small molecules."
Virtually sneaking up on the RNAi space with late-stage ophthalmology and renal therapies.
"Quark continues to advance its two pivotal Phase 3 studies and one Phase 2 study of RNAi-based therapeutics for kidney and eye indications. In the second half of 2017, Quark expects to announce:
- Results of its Phase 2 study of QPI-1002 for the prevention of acute kidney injury in patients undergoing major cardiovascular surgery.
- An interim analysis of its Phase 2/3 study of QPI-1007 for the preservation of visual acuity in acute nonarteritic ischemic optical neuropathy, or NAION."
Pushing preclinical testing of molecules to correct protein misfolding in cataracts and other conditions by preventing and reversing aggregation of alpha crystallin.
"ViewPoint Therapeutics is making progress as planned. In 2017, the company will continue to carry out preclinical studies on its lead candidate, VP1-001, as well as secondgeneration molecules targeting alpha-crystallin for the treatment of cataracts and presbyopia."
Completing a Phase 2 trial and hoping to launch a pivotal Phase 3 trial of its lead drug in DMD, with clinical data set for release this year.
"Catabasis has continued to make significant progress. The company held its first Investor Day on Nov. 17, 2016, on edasalonexent (CAT-1004), for the treatment of Duchenne muscular dystrophy (DMD), and its rare disease pipeline. This event included guest speakers Craig McDonald, M.D., and H. Lee Sweeney, Ph.D., in addition to the Catabasis executive team. Catabasis presented the MoveDMD trial design and their expectations for the upcoming important clinical trial results on their lead program in early 2017. In the first half of Q1 2017, the company expects to report topline safety and efficacy results from the placebo-controlled portion of the MoveDMD Phase 2 trial of edasalonexent in DMD. Assuming positive Phase 2 results, Catabasis anticipates initiating two additional clinical trials in DMD next year, a pivotal Phase 3 trial, as well as a trial in nonambulatory patients. Catabasis expects to report periodic results from the ongoing MoveDMD 36-week open-label extension in 2017. There are also additional diseases in which edasalonexent may be beneficial; therefore, Catabasis expects to initiate a Phase 2 trial for an additional rare disease for edasalonexent in Q4 2017 or Q1 2018. The company also discussed the rare disease pipeline, including the recent announcement of CAT-5571, an activator of autophagy, as a potential treatment of cystic fibrosis. Catabasis expects to initiate a Phase 1 trial with CAT-5571 in Q4 2017 or Q1 2018. Preclinical research with CAT-4001 has continued in diseases such as ALS and Friedreich’s ataxia and further research is expected in 2017."