Asana Biosciences LLC was the first to move a dual Janus kinase (JAK) and spleen tyrosine kinase (SYK) inhibitor into the clinic in moderate to severe atopic dermatitis. The company has been rewarded for the effort with an FDA fast track designation for lead candidate ASN-002, which is under investigation in the phase IIb RADIANT (Relief from Atopic DermatitIs with JAK and SYK INhibiTion) study. Asana also is evaluating ASN-002 in a phase II study in individuals with severe chronic hand eczema.

And that's just the tip of the pipeline for the company, of Lawrenceville, N.J., which is advancing additional assets in immuno-inflammatory indications along with a trio of cancer compounds.

Asana was formed in 2014 through the sale of Endo International plc's drug discovery portfolio for an undisclosed up-front payment and potential milestones on the achievement of predetermined development objectives. Sandeep Gupta, Endo's senior vice president of discovery and early development, was named CEO, and Asana's management team was largely populated with Endo alumni, including Roger Smith, vice president of operations, who had more than 30 years of tenure at Endo and other biopharmas; Niranjan Rao, vice president of clinical development, who was Endo's vice president of clinical pharmacology, drug metabolism and pharmacokinetics; and Scott Thompson, senior director of pharmaceutical development, who was Endo's director of medicinal chemistry.

"All of our molecules were discovered by the Asana team," Gupta told BioWorld.

Operating with just 17 full-time employees, Asana continued to develop and fully owns its programs. In addition to ASN-002, follow-on candidate ASN-008, a topical sodium ion channel blocker that is selective for itch and pain sensing neurons, is being advanced to treat chronic pruritus, pain and atopic dermatitis. In animal studies, the asset showed rapid onset and duration of action following a single application. The molecule is expected enter the clinic in early 2019.

A third immunology asset, ASN-011, a small-molecule cytokine signaling pathway inhibitor designed to treat autoimmune diseases, remains in discovery.

In oncology, Asana's most advanced agent is ASN-003, a selective inhibitor of BRAF and PI3 kinases. Asana, which postulates that dual targeting of those pathways has the potential to overcome or delay acquired resistance to selective RAF inhibitors, has an ongoing phase I study of the agent in individuals with BRAFV600-mutated metastatic melanoma, metastatic colorectal cancer or advanced non-small-cell lung cancer and advanced solid tumors with documented PIK3CA mutation. The open-label, parallel-assignment trial is expected to enroll approximately 100 participants, with data expected in 2020, according to Cortellis Clinical Trials Intelligence. Part A of the trial is assessing maximum tolerated dose as the primary endpoint, while part B is evaluating overall disease status using the RECIST 1.1 criteria.

ASN-007, also in phase I development, is an inhibitor of the extracellular-signal-regulated kinases ERK1 and ERK2, key players in the RAS/RAF/MEK/ERK (MAPK) signaling pathway. The open-label, dose-finding study expects to recruit approximately 110 participants with advanced solid tumors, including BRAF- and KRAS-mutant cancers, with similar co-primary endpoints as the ASN-003 trial and data also due in 2020, according to Cortellis.

Expecting to reach the clinic next year is ASN-004, an antibody-drug conjugate that targets the 5T4 oncofetal antigen, which is expressed in a wide range of malignant tumors but with limited expression in normal tissues. In human tumor xenograft models, ASN-004 showed antitumor activity following a single administration.

Asana has maintained development momentum through its "strong and focused" investor base, which includes Chirag and Chintu Patel, the co-founders and co-chairs of Amneal Pharmaceuticals LLC, and a West Coast family office. Although an IPO could be in Asana's future at some point, the company is "well funded to take phase I programs to at least proof of concept," Gupta said, observing that markets have been "a little choppy" of late. (See BioWorld, Dec. 10, 2018.)

A bigger question for Asana is how much the company can prosecute on its own and where it should look for partnerships.

"We always entertain potential collaborations," Gupta said, "but that's not something we will do prematurely. We'll do it with the right inflection point and the right partner. We realize we have a large portfolio and we're a small company, but we're not in a rush to out-license anything unless it makes sense for us."

'A differentiated strategy for each program'

Asana's development strategy may make sense for multiple suitors. In atopic dermatitis, for instance, where other inhibitors are JAK-selective, "our belief is that the disease is multifactorial, involving multiple pathways," Gupta explained. "Because of our activity toward both the JAK and SYK kinase pathways, we target a broader spectrum of cytokines, so we're able to get good efficacy along with a strong safety profile for the molecule. In addition to working systemically on the lymphocytes and the blood cells, we also have very strong activity on the epithelial cells and keratinocytes, which also differentiates us, to some extent, from other molecules."

In January, Asana reported that ASN-002 achieved efficacy in a double-blind, placebo-controlled, dose-ranging phase Ib proof-of-concept study that enrolled 36 individuals with moderate to severe atopic dermatitis. Following four weeks of treatment, nearly all patients obtained 50 percent improvement in disease severity with oral dosing of 40 mg and 80 mg once daily and showed substantial decreases in patient-reported itch measured by Numeric Rating Scale. Individuals who received ASN-002 were more likely to improve to 0-1 in Investigator's Global Assessment relative to those who received placebo, and ASN-002 was associated with a reduction of body surface area of skin involvement. In addition, the study drug showed dose-dependent exposure in patients and caused reductions in several serum inflammation biomarkers, including cytokines.

The company plans to present additional data this week at the Inflammatory Skin Disease Summit in Vienna.

JAK inhibitors are a common theme in atopic dermatitis. Olumiant (baricitinib), the JAK1/2 inhibitor from Eli Lilly and Co. and licensor Incyte Corp. approved this year to treat moderately to severely active rheumatoid arthritis, is in phase III development, but its safety profile first led to a complete response letter, a challenging bout with members of the Arthritis Advisory Committee and, ultimately, a black box warning, giving pause in the atopic dermatitis indication. (See BioWorld, June 4, 2018.)

Abbvie Inc. has the JAK1 upadacitinib in phase III U.S. development in the indication along with rheumatoid arthritis, ulcerative colitis, psoriatic arthritis and Crohn's disease. Pfizer Inc. has advanced the JAK1 PF-04965842 into phase III in atopic dermatitis, as well, though the New York-based pharma abandoned it in other indications, according to Cortellis. Four JAK inhibitors, in addition to ASN-002, are in phase II trials, with two others in discovery.

"JAK inhibitors, in general, have not been facing any major challenges from an efficacy perspective," Gupta said. Problems in the space, such as those that thwarted Realm Therapeutics plc, "are mainly coming from other mechanisms," he maintained. (See BioWorld, Aug. 15, 2018, and Sept. 18, 2018.)

Provided data from the phase IIb trial of ASN-002, due next year, are positive, fast track status gives Asana more leverage to meet with the FDA to design a pivotal program. Indeed, the company plans to begin preparing soon for the potential phase III and expects to run at least two trials, "but we're looking forward to continuing to have more interactions with the FDA" for specific guidance, Gupta said.

The company also is working with the EMA in preparation for filings with multiple regulatory agencies.

Asana, loosely translated as "seat of respect" in Sanskrit and a common yoga posture, has no intention of slowing its pace.

"We work on validated targets, but we do have a differentiated strategy for each program in mind, which we cultivate very early on, in the discovery phase itself," Gupta said. "When we come with a second or third or fourth product in the market, our compounds offer a value proposition that will help the patients, the providers and the payers to get behind these products."