4D Molecular Therapeutics Inc., of Emeryville, Calif., said it enrolled the first participant in its Choroideremia Natural History Study, for use in developing a gene therapy product optimized for intravitreal administration to treat choroideremia patients. 4DMT has deployed its AAV vector discovery platform, Therapeutic Vector Evolution, to create and optimize an AAV vector for intravitreal delivery to the retina.

Aeterna Zentaris Inc., of Charleston, S.C., said the confirmatory phase III study of Macrilen (macimorelin), conducted to resolve outstanding issues in an FDA complete response letter, failed to achieve its objective of validating a single oral dose of macimorelin for the evaluation of growth hormone deficiency in adults, using the insulin tolerance test as a comparator. The company said it is evaluating the outcome of the trial and will determine in the near future whether it will continue with the development of Macrilen. In the meantime, it plans to redirect resources to the completion of the ongoing phase III trial of Zoptrex (zoptarelin doxorubicin) in women with advanced, recurrent or metastatic endometrial cancer who have progressed and who have received one chemotherapeutic regimen with platinum and taxane (either as adjuvant or first-line treatment). Shares of Aeterna (NASDAQ:AEZS) fell 65 cents, or 17.8 percent, to close Thursday at $3. (See BioWorld Today, Nov. 7, 2014.)

Aridis Pharmaceuticals Inc., of San Jose, Calif., reported results from its phase I/IIa study of AR-301, its fully human monoclonal antibody against Staphylococcus aureus alpha-toxin, which is being evaluated as an adjunctive therapy in combination with standard-of-care antibiotics for hospital-acquired pneumonia and ventilator-associated pneumonia. The double-blind, placebo-controlled study met its primary endpoint of safety. Aridis will move forward with plans for late-stage clinical studies of AR-301 in 2017.

Arno Therapeutics Inc., of Flemington, N.J., said it decided not to enroll the remaining three patients in the company's ongoing phase II trial of onapristone, a progesterone receptor antagonist, in combination with Zytiga (abiraterone acetate, Johnson & Johnson) in men with advanced castration-resistant prostate cancer (CRPC) who have failed Zytiga alone. The protocol requires an efficacy review after the enrollment of 18 patients. To date, 15 patients have been enrolled, and the company does not believe the data collected from the first 12 patients in the study justifies the enrollment of additional subjects. The company said its decision was not based on any safety signal and it will continue to monitor all patients currently enrolled in the trial.

Celyad SA, of Mont-Saint-Guibert, Belgium, said the first patient started cell processing for its phase Ib trial testing immunotherapy NKR-2. The first CAR-T NKR-2 dose level infusion (3x108 cells) is expected this month. The study, dubbed THINK, will test the safety and clinical activity of multiple administrations of autologous CAR T NKR-2 cells in seven refractory cancers, including five solid tumors (colorectal, ovarian, bladder, triple-negative breast and pancreatic cancers) and two hematological tumors (acute myeloid leukemia and multiple myeloma). The dose-escalation part of the study will enroll up to 24 patients, while the extension phase would enroll 86 additional patients.

CTI Biopharma Corp., of Seattle, said the FDA removed the full clinical hold, implemented in February, for the IND for pacritinib. The new trial, PAC203 plans to enroll up to about 105 patients with primary myelofibrosis who have failed prior Jakafi (ruxolitinib, Incyte Corp.) therapy to evaluate the safety and the dose-response relationship for efficacy (spleen volume reduction at 24 weeks) of three dose regimens: 100 mg once daily, 100 mg twice daily (BID) and 200 mg BID. The 200-mg BID dose regimen was used in PERSIST-2. The company expects to start the trial in the second quarter of 2017. Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. Shares of CTI (NASDAQ:CTIC) gained 49 cents, or 12.3 percent, to close Thursday at $4.46. (See BioWorld Today, Feb. 9, 2016.)

Enterome SA, of Paris, said it started a phase I trial with lead small-molecule drug candidate EB8018, which is designed to block FimH, as a potential treatment for Crohn's disease. The study is designed to determine the safety and tolerability profile of single and multiple doses of EB8018 in healthy subjects. It will also assess the pharmacokinetic profile of single and multiple doses and the effects of EB8018 on the healthy gut microbiome. In parallel with the phase I study, Enterome is developing a non-invasive microbiome biomarker to identify patients that may benefit from treatment with EB8018.

Fate Therapeutics Inc., of San Diego, said the first patient was treated in its PROTECT phase I/II trial of Protmune, a next-generation hematopoietic cell graft, for the prevention of acute graft-vs.-host disease (GVHD). The phase I stage will assess the safety of Protmune in up to 10 subjects, while the randomized, controlled phase II stage is intended to assess the efficacy of Protmune in 60 subjects. The primary endpoint is cumulative incidence of acute GVHD by day 100 following hematopoietic cell transplant. Other key endpoints include cumulative incidence of severe infections, cancer relapse, event-free survival and overall survival.

Gemphire Therapeutics Inc., of Livonia, Mich., updated its clinical programs for gemcabene, a liver-directed drug designed to reduce apoC-III mRNA and plasma levels and may also inhibit acetyl-CoA. The phase IIb ROYAL-1 trial is more than 90 percent to its target enrollment and is testing gemcabene in hypercholesterolemia patients not adequately controlled on high-intensity or moderate-intensity stable statin therapy. The company now expects top-line data in the third quarter of this year. Gemphire also expects to report interim results for its open-label COBALT-1 trial testing gemcabene in patients with clinically diagnosed homozygous familial hypercholesterolemia during the week of Jan. 30. Top-line results from the INDIGO-1 in severe hypertriglyceridemia are expected in the fourth quarter.

Genocea Biosciences Inc., of Cambridge, Mass., reported results from a planned interim analysis of its phase IIb trial of GEN-003 in genital herpes infections, showing that, at six months after dosing, the T-cell-directed immunotherapy demonstrated statistically significant improvements vs. placebo across multiple clinical endpoints. The 60 mcg per antigen/ 50 mcg of adjuvant dose of GEN-003 significantly reduced the rate of genital lesions during the six months following dosing compared to placebo (4.5 percent of days vs. 7.9 percent, respectively; 41 percent reduction vs. placebo, p < 0.05). GEN-003 also consistently demonstrated significant benefits vs. placebo across several other clinical endpoints across the dose groups. Results continue to support the selection of the 60 mcg per antigen/50 mcg of adjuvant dose for the planned phase III program, expected to start in the fourth quarter of this year, the company said.

Heron Therapeutics Inc., of San Diego, reported top-line results from its phase II study of long-acting anesthetic HTX-011 in subjects undergoing abdominoplasty (Study 203), demonstrating statistically significant reductions in both pain intensity and the use of opioid rescue medications through 96 hours following surgery. The trial tested the locally administered drug for postoperative anesthesia following abdominoplasty surgery. The Summed Pain Intensity score through 96 hours post-surgery (SPI 0-96) was significantly reduced with HTX-011 and produced a statistically significant 36.6 percent reduction in pain through 96 hours following surgery, as measured by SPI 0-96 (p=0.0104). Pain was consistently reduced through 96 hours with statistically significant reductions observed between 24 hours to 48 hours (p=0.007), 48 hours to 72 hours (p=0.038) and 72 hours to 96 hours (p=0.016) after a single administration of HTX-011.

Janssen Biotech Inc., of Horsham, Pa., said it plans to evaluate a combination of Darzalex (daratumumab) and the checkpoint inhibitor Opdivo (nivolumab, Bristol-Myers Squibb Co.) in phase Ib/II studies in multiple myeloma (MM) and several solid tumor types. Studies are expected to start this year. The MM study will evaluate the safety and tolerability of the combination with or without (Pomalyst (pomalidomide, Celgene Corp.) and dexamethasone in relapsed/refractory MM. The solid tumor studies will evaluate the safety, tolerability and clinical benefit of the combination in patients with advanced or metastatic tumors, including non-small-cell lung, head and neck, pancreatic, colorectal and triple-negative breast cancers. No financial terms of the collaboration were disclosed. Additional tumor types may also be evaluated. Janssen has an exclusive license on Darzalex from Genmab A/S, of Copenhagen.

Keystone Nano Inc., of State College, Pa., said the FDA approved its IND to test Ceramide Nanoliposome in a phase I/II trial in solid tumors. The trial will enable the company to establish a safe dose level and begin gathering information about the efficacy of the product as a cancer therapy. The phase I portion will establish dosing and safety, while the phase II component will focus on liver cancer. Keystone Nano previously said it was awarded a $2 million Phase II Small Business Innovation Research grant from the National Cancer Institute, which is funding part of this trial.

Lipocine Inc., of Salt Lake City, said it plans to start a dosing flexibility study in addition to its previously announced dosing validation study for LPCN 1021, an oral testosterone product candidate for testosterone replacement therapy in adult males for hypogonadism. The flexibility study will assess LPCN 1021 in hypogonadal males on a fixed daily dose of 450 mg divided into three equal doses. The validation study is assessing the impact of LPCN 1021 in hypogonadal males on a fixed daily dose of 450 mg divided into two equal doses. Lipocine expects resubmission of the LPCN 1021 NDA to the FDA to contain data from both studies. The company received a complete response letter in June.

Lixte Biotechnology Holdings Inc., of East Setauket, N.Y., said phase I results of its cancer compound, LB-100, were published online in Clinical Cancer Research. Findings showed that 10 (46.7 percent) of 21 patients who received at least two cycles of LB-100, a small-molecule inhibitor of protein phosphatase, achieved stable disease without limiting toxicity for up to 15 cycles of therapy, including one patient with pancreatic cancer who had a partial regression.

Minervax ApS, of Copenhagen, reported results from a phase I trial in 240 healthy adult women with its protein-only group B Streptococcal infections (GBS) vaccine. The vaccine targets pregnant women for the prevention of life-threatening infections in newborns. The vaccine proved to be well-tolerated and highly immunogenic, with a safety profile similar to that of other protein vaccines administered with Alhydrogel adjuvant. Analysis of individual responses revealed that about 50 percent of subjects reached the maximum antibody titer already after the first dose, whereas the remaining 50 percent benefited from a second dose. However, the latter group still reached in excess of 30-fold increases over pre-immune levels already after the first dose. The antibody responses obtained in the immunized individuals were highly functional, being capable of inducing opsonophagocytic killing of and inhibiting epithelial cell invasion by both laboratory and clinical isolates of GBS.

Monosolrx Inc., of Warren, N.J., said the FDA accepted its IND application for Riluzole Oral Soluble Film (Riluzole OSF) for the treatment of amyotrophic lateral sclerosis (ALS). The accepted IND outlines Monosol's clinical development plans for Riluzole OSF for the treatment of ALS. Riluzole is a glutamine blocker currently available in a tablet formulation. It has been shown to delay the onset of ventilator dependence or tracheostomy in select ALS patients, and may increase survival by two to three months. Its use has also been studied in mood and anxiety disorders as well as Alzheimer's disease.

Nicox SA, of Sophia Antipolis, France, updated regulatory and clinical activities for NCX 4251, its ophthalmic suspension of fluticasone propionate nanocrystals being developed as a topical treatment for acute exacerbation of blepharitis. Based on feedback from the recent pre-IND meeting with the FDA, Nicox said it is finalizing the design of a phase II trial testing NCX4251 vs. a vehicle comparator in patients with acute exacerbation of blepharitis. The dose-ranging trial will measure the clinically relevant difference in the proportion of subjects with clinical cure (defined as the absence of lid margin redness, lid debris and lid discomfort) obtained with each dose of NCX 4251 vs. vehicle as the primary endpoint. The study is set to start in the fourth quarter.

Novaliq GmbH, of Heidelberg, Germany, reported phase II results showing that Cyclasol, a clear, preservative-free cyclosporine A solution, showed a consistent reduction in corneal fluorescein staining, the primary sign endpoint, with an early onset of action over the four-month treatment period. The trial enrolled 207 patients with moderate to severe dry eye disease.

Ocera Therapeutics Inc., of Palo Alto, Calif., reported results from a phase I trial of oral OCR-002 (ornithine phenylacetate) in patients with cirrhosis, showing favorable oral absorption and pharmacokinetics in the intended population. Ocera is developing OCR-002 for chronic use to maintain remission of hepatic encephalopathy, a neurocognitive disorder associated with serious liver disease. A phase IIa study in cirrhotic patients is planned to start in the first half of this year.

Otonomy Inc., of San Diego, reported results from its pivotal phase III trial of Otiprio (ciprofloxacin otic suspension) in patients with acute otitis externa, also known as swimmer's ear, showing that the single-administration trial met the primary endpoint by showing a statistically significant increase in clinical cure rate compared to sham at day eight (p<0.001). Treatment with Otiprio was also well-tolerated. Based on those results, Otonomy expects to submit a supplemental NDA in the first half of 2017. Otiprio, an antibacterial, previously gained approval for use in pediatric patients undergoing ear tube placement surgery. (See BioWorld Today, Dec. 14, 2015.)

Pfizer Inc., of New York, said its comparative, confirmatory REFLECTIONS B538-02 study met its primary objective by demonstrating equivalent efficacy as measured by ACR20 response rate at week 12. The trial tested the safety and immunogenicity of PF-06410293 compared to Humira (adalimumab, Abbvie Inc.), each taken in combination with methotrexate, in patients with moderate to severe rheumatoid arthritis. PF-06410293 is being developed as a potential biosimilar to Humira.

PTC Therapeutics Inc., of South Plainfield, said its joint development program in spinal muscular atrophy (SMA) with Roche Holding AG, of Basel, Switzerland, and the SMA Foundation initiated a clinical study in infants with type I SMA. The study, named FIREFISH, will investigate the safety, tolerability and efficacy of RG7916 in babies, 1 to 7 months. RG7916 is an oral small-molecule splicing modifier that directly targets the underlying molecular deficiency of SMA by modulating SMN2 splicing to increase expression of stable full-length SMN protein from the SMN2 gene. The primary objective of part one of the study is to assess the drug's safety profile and determine the dose for part two, which will enroll about 40 infants and assess efficacy over a 12-month period.

Sangamo Biosciences Inc., of Richmond, Calif., said the FDA cleared the IND for its SB-525 gene therapy program for the treatment of hemophilia A.

Seattle Genetics Inc., of Bothell, Wash., said it enrolled the first patient in a phase I trial of SGN-CD352A, a CD352-targeted antibody-drug conjugate, for patients with relapsed or refractory multiple myeloma (MM). The trial is designed to assess the safety and antitumor activity of the drug as a single agent and will be conducted in two parts, with a dose-escalation part to identify the maximum tolerated dose of SGN-CD352A followed by an expansion part to further define safety and antitumor activity. SGN-CD352A will be administered every four weeks, and the study will enroll about 75 relapsed or refractory MM patients.

Synthetic Biologics Inc., of Rockville, Md., reported top-line data from its phase IIb trial of SYN-004 (ribaxamase), its oral enzyme designed to protect the gut microbiome from disruption caused by certain intravenous beta-lactam antibiotics. The randomized, double-blind, placebo-controlled trial of 412 patients, met its primary endpoint of significantly reducing C. difficile infection (CDI). Preliminary analysis of the data indicated seven confirmed cases of CDI in the placebo group compared to two cases in the ribaxamase treatment group. Patients receiving ribaxamase achieved a 71.4 percent relative risk reduction (p=0.045) in CDI rates compared to patients receiving placebo. Adverse events reported during the trial were comparable between treatment and placebo arms.

Tyme Technologies Inc., of New York, said it started enrolling subjects in the second stage of its phase Ib/II open-label trial using monotherapy SM-88 treatment for progressive prostate cancer. That follows preliminary data from the first stage of the trial in safety and circulating tumor cells at both dosage levels. During the second stage, the company expects to enroll an additional 30 subjects for up to six months. In addition to safety and tolerability, it will further evaluate SM-88's previously reported antitumor activity in prostate cancer, determined by improving PSA levels and radiographic-determined tumor response. The trial also includes secondary endpoints evaluating correlative measures and biomarker indicators, including circulating tumor cells, testosterone levels and quality of life.

Viamet Pharmaceuticals Inc., of Research Triangle Park, N.C., reported that the phase IIb RENOVATE (REstoring Nail; an Oral VT-1161 Tablet Evaluation) trial of VT-1161 in onychomycosis of the large toenail and the phase IIb REVIVE (REcurrent Vulvovaginal Candidiasis Inhibition: An Oral VT-1161 Tablet Evaluation) trial of VT-1161 to treat recurrent vulvovaginal candidiasis met their primary endpoints. In the RENOVATE study, the intent-to-treat analysis showed that treatment with VT-1161 resulted in complete cure rates ranging from 32 percent to 42 percent at 48 weeks across four study arms compared to 0 percent for placebo. All treatment arms achieved statistical significance vs. placebo. In the per-protocol analysis, which included patients evaluable through week 48, cure rates were as high as 55 percent in the VT-1161 groups. An 87 percent median reduction in the percentage of nail involvement was seen at week 48 across the VT-1161 arms compared to a 9 percent reduction in the placebo arm. Complete cure rates continued to improve through week 60. REVIVE showed that the proportion of patients treated with VT-1161 who had one or more culture-verified episodes of vaginal yeast infection through 48 weeks was 0 percent to 11 percent across the four study arms compared to a recurrence rate in the placebo arm of 66 percent. All arms of the study achieved statistical significance vs. placebo. In both studies, VT-1161 was well-tolerated with a favorable safety profile. The company plans to present full results from the studies at an undisclosed scientific conference. Lead candidate VT-1161 is a highly potent and selective orally available inhibitor of fungal CYP51.

Xigen SA, of Geneva, said phase II results published online in the American Journal of Ophthalmology showing that brimapitide (XG-102) demonstrated noninferiority, when given as a single subconjunctival injection, at the end of surgery compared to dexamethasone administered four times a day for 21 days. It also showed safety and good tolerability when administered directly into the eye. Brimapitide is designed to inhibit the c-Jun N-Terminal kinase.

Zosano Pharma Corp., of Fremont, Calif., said the last subject was treated in the company's registration-enabling, pivotal trial (Zotrip) of M207, a zolmitriptan-coated microneedle patch, for migraine. The double-blind, randomized, placebo-controlled trial is comparing three doses of M207 (1 mg, 1.9 mg and 3.8 mg) to placebo for the treatment of a single migraine attack. The co-primary endpoints are the proportion of subjects with pain freedom at two hours post-dosing, and the proportion of subjects with freedom from their most bothersome symptom at two hours post-dosing.