Cara Therapeutics(US:CARA)2019-05-07 21:01Product Development and Trials - KORSUVA (CR845/difelikefalin) injection has shown statistically significant reductions in itch intensity in Phase 2 trials for hemodialysis patients with moderate-to-severe CKD-associated pruritus (CKD-aP) and is currently in Phase 3 trials[170]. - KORSUVA (CR845/difelikefalin) injection has received Breakthrough Therapy Designation from the FDA in June 2017, indicating its potential in treating CKD-aP[179]. - The product candidate pipeline includes ongoing Phase 3 trials for KORSUVA (CR845/difelikefalin) injection in CKD-aP and Phase 2 trials for Oral KORSUVA in CKD and chronic liver disease[179]. - The first pivotal Phase 3 efficacy trial of KORSUVA (CR845/difelikefalin) injection for CKD-aP treatment in hemodialysis patients was initiated in Q1 2018, with top-line data expected in Q2 2019[182]. - KALM-1 Phase 3 trial enrolled over 350 hemodialysis patients across approximately 60 clinical sites, with top-line data expected in Q2 2019[184]. - The second Phase 3 trial (KALM-2) began in August 2018, aiming to enroll patients in the U.S. and multiple countries, with top-line data expected in H2 2019[185]. - A 52-week Phase 3 safety trial initiated in Q2 2017 is evaluating KORSUVA injection's long-term safety, with approximately 150 patients having completed at least six months of treatment[186]. - A new open-label Phase 3 safety trial was initiated in Q2 2019, expected to enroll up to 400 hemodialysis patients[187]. - The Phase 2 trial of Oral KORSUVA for CKD patients began in July 2018, with top-line data expected in H2 2019[194]. - The investigational new drug application for Oral KORSUVA for chronic liver disease-associated pruritus was submitted in Q4 2017, with a Phase 1 trial completed[198]. - A multi-dose Phase 2 trial for Oral KORSUVA in atopic dermatitis is expected to be initiated around mid-2019[201]. - CR845/difelikefalin is being investigated for acute postoperative pain relief, designed to avoid mu opioid receptor stimulation[202]. - CR845/difelikefalin injection achieved statistical significance for pain relief over 24 hours with the 1.0 mcg/kg dose versus placebo (p=0.032)[204]. - The Phase 2b trial of Oral CR845/difelikefalin showed a statistically significant 39% reduction in mean joint pain score for patients with OA of the hip on the 5.0 mg dose (p=0.043)[216]. Financial Performance - Total revenue recognized to date is $5.3 million from clinical development or regulatory milestone payments and sub-license fees[219]. - Total revenue for the three months ended March 31, 2019, was $4.38 million, a 100% increase compared to the same period in 2018[231]. - License and milestone fees revenue was $4.24 million for the three months ended March 31, 2019, with no revenue reported for the same period in 2018[232]. - Research and development (R&D) expenses totaled $23.61 million for the three months ended March 31, 2019, representing a 76% increase from $13.43 million in 2018[234]. - Direct clinical trial costs increased to $17.74 million, a 90% rise compared to $9.35 million in the prior year[234]. - Other income increased to $1.09 million for the three months ended March 31, 2019, a 250% increase from $311,000 in 2018[238]. - General and administrative expenses for the three months ended March 31, 2019, were $3.91 million, a 6% increase from $3.70 million in 2018[237]. - Net losses for the three months ended March 31, 2019, were $22.0 million, compared to $16.8 million for the same period in 2018, with an accumulated deficit of $316.3 million as of March 31, 2019[256]. Cash and Capital Management - The company had $156.1 million in unrestricted cash and cash equivalents as of March 31, 2019, sufficient to fund operations into Q4 2020[248]. - The company expects existing cash and cash equivalents will be sufficient to fund anticipated operating expenses into the fourth quarter of 2020[264]. - The company may need to raise additional capital to meet development objectives, particularly for I.V. and Oral CR845/difelikefalin, which could dilute existing stockholders' ownership[263]. - The company plans to use proceeds from its recent underwritten offering to fund clinical trials and research development activities, including Phase 3 programs for KORSUVA[246]. - As of March 31, 2019, the company had invested $142.0 million in marketable securities with a yield of approximately 2.65%[281]. - Net cash used in operating activities for the three months ended March 31, 2019, was primarily due to a net loss of $22.0 million and cash outflows from changes in operating assets and liabilities totaling $3.3 million[269]. - Net cash provided by investing activities was $26.4 million for the three months ended March 31, 2019, mainly from maturities of available-for-sale marketable securities[273]. Risks and Uncertainties - The successful development of product candidates is highly uncertain, with numerous risks associated with clinical trials and regulatory approvals[260]. - The company has incurred significant operating and net losses since inception, with expectations to continue incurring such losses in the near future[256]. - The anticipated operating expenses will increase due to ongoing development of KORSUVA (CR845/difelikefalin) injection and Oral KORSUVA, as well as the establishment of sales and marketing infrastructure[257]. - The safety profile of CR845/difelikefalin injection was generally well tolerated across multiple studies with no clinically significant changes in ECG characteristics[209]. - The most common adverse events reported for CR845/difelikefalin included dizziness (8%), headache (6%), dry mouth (6%), and constipation (12%)[216]. - CR845/difelikefalin injection demonstrated no significant respiratory safety events in a Phase 1 trial with 15 healthy volunteers[212]. - The company does not intend to develop Oral CR845/difelikefalin for OA pain independently and will seek potential partners for further development[218]. Regulatory and Collaboration Efforts - The company has filed a shelf registration statement for aggregate offerings of up to $300 million to fund future operations and clinical trials, effective since April 4, 2019[175]. - The company retains all rights to KORSUVA (CR845/difelikefalin) in the United States and will promote it in U.S. dialysis clinics under a profit-sharing agreement with VFMCRP[170]. - The company aims to establish additional collaborations for its product candidates to enhance commercialization efforts[163]. - The company is eligible for up to $470 million in regulatory and commercial milestone payments under the VFMCRP Agreement[250]. - Under the Maruishi Agreement, the company could earn up to $6.0 million in clinical development milestones and $4.5 million in regulatory milestones[251].