Companies To Watch: A Roundup Of Life Science Developments And Technologies

By Wayne Koberstein, executive editor

Each month, Companies to Watch spotlights one company that has received scant press coverage but, nonetheless, contains an especially interesting story. At the end of this past year, we thought it would be useful to check in on our 2013 Companies to Watch with a “roundup of updates” on how all of the companies have fared since our coverage. We contacted each company, asking for responses to three questions:

• What have been the most important developments for your company since it was featured in the ___ 2013 edition of Life Science Leader’s Companies to Watch?
• How would you summarize, in a single quotable sentence, the present status of the company in light of those developments?
• What developments or milestones do you anticipate in 2014?

We received full responses from 11 of the 12 Companies to Watch featured in 2013. Their input varied from highly cautious and formal to genuinely “excited.” Together with our own brief summaries of the companies’ progress, we offer their assessments and updates here, in our 2013 Companies to Watch Roundup. (Company statements appear in quotes.)

January — Acetylon
Careful target selection — meant to help surround and overcome tumor cells’ defenses by cutting off one of two pathways they use to degrade waste proteins — was the theme of our CtW analysis of Acetylon early last winter. Since then, the tune has changed to following up on promising clinical data — and with a new strategic partner. President and CEO Walter Ogier summarizes the company’s current status: “Acetylon is capitalizing on its recent agreement with Celgene and the positive activity we’ve seen in clinical and preclinical studies to date by significantly expanding our clinical program for selective HDAC6 inhibitor, ricolinostat, with advancement of our ongoing trials plus new combinations in multiple myeloma and a new indication, lymphoma.”

DEVELOPMENTS TO DATE

• July: Acetylon entered into an exclusive strategic collaboration with Celgene, structured with $100 million payment up front, a minimum $500 million future cash purchase price if or when Celgene exercises its option to acquire, plus up to $1.1 billion in regulatory and sales milestones.
• December: Reported that its selective HDAC6 inhibitor, ricolinostat (ACY-1215), showed “striking” signs of therapeutic activity in its Phase 1b trial in combination with Revlimid (lenalidomide) and dexamethasone for the treatment of relapsed or refractory multiple myeloma. In the interim data, 69 percent of patients reported partial or better response. Positive results on ricolinostat also came from interim data in a Phase 1b trial in combination with Velcade and dexamethasone, as a single agent in lymphoma, and in separate combinations treating either multiple myeloma or lymphoma: with each of three proteasome inhibitors; with two PI3K inhibitors; and with a Bruton’s tyrosine kinase inhibitor.

COMING IN 2014

• initiation of two additional clinical trials of ricolinostat for the treatment of multiple myeloma in combination with standard-of-care drugs
• initiation of a clinical trial of ricolinostat for the treatment of lymphoma
• completion of the Phase 1b portion of the currently ongoing trials in combination with Revlimid and Velcade and initiation of Phase 2 clinical development

February — Auspex
Gone dark. Not officially, but for all practical purposes, this developer of deuterium-based compounds has ceased shedding light on itself for journalists. Repeated attempts to contact the company about this report went unanswered. The long-time PR person for the company was let go a few weeks after a major management turnover. In October, Pratik Shah replaced former CEO Larry Fritz, who left at mid-year. At the same time, the company replaced the COO and CFO, and it added a “chief development officer.” The company has issued no press releases or public statements since that time. The following comes from limited public disclosures:

DEVELOPMENTS TO DATE

• March: Square 1 Bank granted a terms loan, or “credit facility,” to Auspex to help fund Phase 3 clinical trials for its lead compound SD-809.
• July: initiation of Phase 3 Trial of SD-809 for treating chorea associated with Huntington’s disease, with opportunities in two additional indications, tardive dyskinesia and Tourette’s syndrome
• October: major management turnover; replaced most of the management team including the CEO, and added new officers

March — Centyrex
A company inside a company. Much of J&J’s pharma group consists of small units enveloped or overlapped with other parts of the organization. Centyrex has been an exception. It’s an entrepreneurial business more or less making it on its own as any other bio start-up. But having developed its novel molecular- scaffold Centyrin platform to the point of creating original products, it is becoming more integrated into the Janssen R&D Biotechnology Center of Excellence (BCE). Summarizing the company’s progress, CEO Robert Hayes says, “Centyrex has delivered on its goals to develop a therapeutic platform that complements the strengths Janssen R&D has in monoclonal antibodies.” The company remains vague about the therapeutic areas and entities it is pursuing, as reflected in its responses for the CtW Roundup below.

DEVELOPMENTS TO DATE

• “making good progress on therapeutic targets in the oncology space”
• “Janssen R&D made the decision to continue support of the Centyrex venture by transitioning the technology into the Janssen R&D BCE and expanding the use of the Centyrin platform.” That means Centyrex will essentially feed the pipeline with newer, early-stage products, handing them off to the BCE at the clinical development stage. The BCE has also assumed responsibility for Centyrin products already in development, as well as taking in a handful of Centyrex employees.

COMING IN 2014

• “We look forward to further studying and progressing our work in oncology. We also look forward to applying the Centyrin technology to targeted therapies that have increased safety and efficacy.”

April — StemCells
“Things are now starting to get really interesting,” says CEO Martin McGlynn about the company’s new-year status. He cites early clinical data from trials of its proprietary purified human neural stem cells (HuCNS-SC) in spinal cord injury, dry AMD (age-related macular degeneration), Pelizaeus-Merzbacher disease (PMD), and Batten disease. “Confirming the extraordinary results seen in the various animal models used to justify the initiation of the clinical trials now underway or already completed.” Phase 2 trials will get underway in 2014, with interim efficacy results planned for mid-2015.

StemCells also recruited some industry veterans, such as Eliseo Salinas, M.D., as EVP R&D; and Greg Schiffman, former CFO of Dendreon. Earlier in the year, the company built and commissioned its own state-of-the-art cGMP cell-processing facility in Sunnyvale, CA. It raised money in several ways, receiving the first tranche ($3.8 million) out of a $19.3 million California Institute for Regenerative Medicine funding of an IND (investigational new drug) for restoration of lost memory in Alzheimer’s disease, a $10 million loan from Silicon Valley Bank, and $25.3 million in equity-based financings.

DEVELOPMENTS TO DATE

• August: Promising two-year data from patients with Pelizaeus-Merzbacher disease (PMD) treated with HuCNSSC cells began showing gains in neurological function and more pronounced myelination compared to year one.
• June – October: Phase 1/2 clinical trial for chronic spinal cord injury was expanded to the U.S. and Canada. Eight of the 12 patients in the current study already have been transplanted in Switzerland.
• September: The FDA approved the expansion of the number of clinical sites from two to five in the company’s Phase 1/2 dry AMD trial and a five-fold increase in the cell dose. Seven of the 16 patients in the study already have been transplanted.

COMING IN 2014

• determine next steps for the advancement of the PMD program
• complete dosing in Phase 1/2 chronic spinal cord injury and dry AMD trials
• initiate controlled Phase 2 chronic spinal cord injury and dry AMD trials
• report data from the current Phase 1/2 spinal cord injury and dry AMD trials

May — Immune Pharmaceuticals
Survival by merger. In the spring when we covered this Israeli developer of in-licensed cancer and inflammation drugs, the company was in the early stages of a merger with troubled EpiCept, primarily with the aim of buying an entry into the U.S. public capital markets. Since then, its focus has been divided between completing the merger — actually structured as a reverse merger — and pushing along its pipeline products: chemo- related pain drug AmiKet and chemokine blocker bertilimumab. Reading between the lines of its roundup responses, it seems the company has made progress on both fronts, as CEO Daniel Teper expresses in this summary of the company’s status: “Immune has the ability to finance through public markets and execute its clinical milestones in 2014 to 2015.”

DEVELOPMENTS TO DATE

• August: closed merger with EpiCept with Immune historical shareholders owning approximately 85 percent of the combined company on a fully diluted basis
• November: listed on OTCQX (New York) and NASDAQ OMX First North Premier (Stockholm)
• During 2013: identified and planned Phase 2 clinical trials for bertilimumab in an orphan indication (Bullous pemphigoid), which will add to the already launched Phase 2 trial in ulcerative colitis

COMING IN 2014

• up-listing to NASDAQ (New York)
• full two-year financing through secondary public offering
• partnering of Phase 3-ready AmiKet with fast-track designation for chemotherapy-induced neuropathic pain
• Phase 2 data for bertilimumab in Bullous pemphigoid, an orphan autoimmune skin disease

June — Cempra
A blockbuster in its pipeline? That was the central question in Cempra’s CtW in mid-2013. Proof is everything, especially for a company that claims it has created both a new class of antibiotics, the “fluoroketolides,” and a new way of delivering them, “loading dose formulation,” exemplified by its lead drug candidate, oral solithromycin. Cempra’s founder, President, and CEO Prabhavathi Fernandes says, “We have reached significant milestones in the second half of 2013, propelling our company to its next stage of development.” On the heels of its June CtW, the company raised $54 million in a public offering of common stock and secured up to $58 million from a BARDA (Biomedical Advanced Research and Development Authority, HHS) drug development contract to develop solithromycin for pediatric use and biodefense.

DEVELOPMENTS TO DATE

• September: Oral and IV solithromycin became the only antibiotic to receive the FDA’s qualified infections product designation (QIPD) for the treatment of CABP (communityacquired bacterial pneumonia). “Solithromycin demonstrated safety and tolerability in patients with chronic liver disease without a change in pharmacokinetics so that there will be no change in dosing of patients with hepatic insufficiency.”
• October: Taksta gained orphan drug designation for the treatment of prosthetic joint infections.
• November: Preclinical results suggested solithromycin may provide effective prevention and treatment of intrauterine infections during pregnancy. “No new antibiotic has been developed for infections in pregnancy in over 20 years.”

COMING IN 2014

• Mid-year: release of Solitaire-Oral Phase 3 trial top-line data in CABP

July — Soligenix

Biodefense drives this company. With U.S. government support, Soligenix continues to develop an anti-ricin vaccine, a treatment for radiation poisoning, and other products based on its ThermoVax platform. In September, it nearly doubled its previous funding with a new $23.6 million BARDA contract and a $6.4 million NIAID (National Institute of Allergy and Infectious Diseases) contract for its radiation drug OrbeShield. Not bad for a company with a tiny market cap of only about $40 million (twice what it was in June). “Now with the proper funding in hand, our primary focus moving into 2014 is on the quality execution of all our development programs,” says Christopher Schaber, chairman, president, and CEO.

DEVELOPMENTS TO DATE

• December: initiated two Phase 2 clinical studies: SGX942, the company’s first-in-class innate defense regulator technology in oral mucositis; and orBec in chronic GI graft-versushost disease (GVHD), supported by a $300 million NIH grant

COMING IN 2014

• initiation of a Phase 2/3 clinical study with SGX203 in pediatric Crohn’s disease and a Phase 2 clinical study with SGX201 in acute radiation enteritis
• completion of oral mucositis Phase 2 clinical study and chronic GI GVHD Phase 2 clinical study
• preclinical data supporting vaccine/biodefense programs, most notably OrbeShield, RiVax (ricin toxin vaccine), and ThermoVax (vaccine heat stabilization technology

August — CogRx (Cognition Therapeutics)
Still a tough cookie in a tough area — this developer of neuroscience drugs for Alzheimer’s disease (AD) and possibly other conditions, such as Parkinson’s and ALS, has been chalking up a series of firsts since its appearance in Companies to Watch. “CogRx’s small molecule drug candidates represent the first ever reported to directly target toxic Abeta oligomer proteins and their receptors and stop their bad effects on memory,” CEO Hank Safferstein says. “CogRx is rapidly advancing these exciting drug candidates toward clinical trials.”

DEVELOPMENTS TO DATE
According to the company, CogRx has:

• become “the first group to demonstrate siRNA (small interfering RNA) knockdown of a specific receptor on neurons and glia; lowers oligomer binding more than 90 percent
• become “the first group to demonstrate dose-dependent reduction in Abeta oligomer binding in post-mortem human AD brain sections using our proprietary small molecule drug candidates and antibodies raised against specific receptor epitopes”
• “developed first-in-class, highly brain-penetrant, orally bioavailable small molecule receptor antagonist (IND candidates) that stop memory deficits in Alzheimer’s disease models”

COMING IN 2014

• conducting a pre-IND meeting with the FDA with the goal of filing an IND by the end of the year
• closing on Series B to fund the AD program into the clinic and into patients diagnosed with Alzheimer’s disease
• “Use of funds will also support further mechanistic work on the soluble Abeta oligomer protein receptor/ receptor complex we have identified and its potential role in other CNS diseases characterized by abnormal protein aggregation”

September — Esperion Therapeutics
On track and on target. Another company with blockbuster potential, and one of the fresh crop of IPOs in 2013, this drug developer aims at the still needy area of cholesterol reduction. Esperion’s strategy is carefully planning studies and trials to prove its concept and define its target patient groups. “We are on track to deliver, in 2014, top-line results from two large robust Phase 2b clinical trials that will transform Esperion into the leading developer of an oral, once-daily, small molecule LDL-C (LDL cholesterol) lowering therapy for the treatment of patients with hypercholesterolemia,” says CEO Tim Mayleben. He says the company set clear goals for its LDL-C lowering drug, ETC-1002, in 2013 and achieved all of them on time

DEVELOPMENTS TO DATE

• October: commenced a large Phase 2b study of ETC 1002 in patients with or without statin intolerance
• November: announced positive Phase 2a results for ETC- 1002 as an add-on to statin therapy
• November: at the American Heart Association meeting, presented positive Phase 2a results in patients with a history of statin intolerance

COMING IN 2014

• initiate robust Phase 2b ETC-1002 add-on to statin therapy study (Q1)
• announce results from two Phase 2b ETC-1002 clinical trials (Q4)
• announce top-line results from nonclinical studies (Q4)
• target several important medical meetings for data presentations (throughout 2014)

October — Inovio
Into and beyond a big partnership. A small-cap player in the cancer vaccine space, Inovio was just beginning its co-development alliance with Roche. Now, as it cements the relationship in clinical trials, the company is thinking even more strongly beyond its first partnering deal, anticipating others on the horizon. Contacted just three months after our coverage of Inovio, CEO J. Joseph Kim explains, “We completed our first Big Pharma partnership and progressed our Phase 3 program to the point of getting data. By all measurements — financial, technical, and clinical — it was a banner year. We expect 2014 to be an even better year and dwarf our 2013 accomplishments.” Kim agrees a large factor in attracting Roche’s interest is the potential of the company’s T-cell targeting and boosting technology in future combination cancer immunotherapies — a potential $35 billion market, as projected by Citibank. Now, he says, Inovio is in “deep discussions” with Roche’s peers in Big Pharma about partnering in that area and others.

DEVELOPMENTS TO DATE

• November — December: completed Roche codevelopment alliance, involving two of Inovio’s clinical-stage products, one (INO-5150) for prostate cancer and the other (INO-1800) for chronic hepatitis B, a common cause of cirrhosis and liver cancer
• Present: In addition to focusing on lead products such as INO-3100 and INO-3112, the company is working with Roche to take INO-5150 to the clinic in a Phase 1 trial. INO- 1800 for chronic hepatitis B is about a year behind.

COMING IN 2014

• First half: launch Phase 1 clinical trial of INO-5150 for prostate cancer, triggering the first milestone payment from Roche
• First half: launch Phase 2 trials of nonpartnered product INO-3112, in advanced cervical and advanced head and neck cancers. Also, run small, uncontrolled exploratory trials to prove comparable T-cell generation in other cancers and bolster the Cellectra Electroporation Delivery Technology platform concept
• Midyear: report results from a current double-blind placebo- controlled Phase 2 efficacy study in cervical pre-cancer involving 150 patients — the first Phase 2 results from the company’s pipeline

November — Vivaldi Biosciences
Victory in a sea of failures. That is Vivaldi’s aim, as it plies its course in developing the only live vaccines among many competing candidates for prevention of pandemic and seasonal flu — namely, its live attenuated influenza vaccines (LAIVs). With few updates since Vivaldi’s end-of-the-year appearance in Companies to Watch, CEO Douglass Given emphasizes the company’s goals for the new year, which include raising more money. “Vivaldi’s strategy to demonstrate clinical proofof- concept for its LAIVs for seasonal and pandemic influenza is realizable with venture financing, and offers investors an attractive valuation, potential for significant ownership, and an exit opportunity through partnering with a pharmaceutical company.” Vivaldi is pursuing a cost-effective means of advancing its LAIV pipeline candidates, hoping to partner for further development and commercialization.

COMING IN 2014

• follow-on investments in Series B financing round
• initiate program to develop a preclinical LAIV candidate for highly pathogenic H7N9 influenza
• advance clinical development of LAIVs for seasonal influenza to address unmet medical needs in elderly and/ or pediatric populations

December — Proteon Therapeutics
Relief for dialysis patients. That is what this developer of a drug to address vascular access failure intends to bestow. The last company to be featured in 2013 Companies to Watch has had scarce time for subsequent developments. But it has plenty of hopes for the new year. “Proteon is preparing to initiate Phase 3 of PRT-201 to address vascular access failure in hemodialysis patients, a serious unmet medical need in an orphan population,” its president and CEO, Timothy Noyes, says modestly. Proteon is currently identifying sites to participate in the Phase 3 trial of PRT- 201 in chronic kidney disease patients undergoing surgical placement of an arteriovenous fistula for hemodialysis. The trial is scheduled for a mid-2014 commencement. About the same time, a Phase 1 trial investigating another application of PRT-201 will yield data.

COMING IN 2014

• secure financing to complete AVF Phase 3
• initiate enrollment in AVF Phase 3
• conclude peripheral artery disease (PAD) trial and report data