Cara Therapeutics is an emerging biotechnology company focused on developing novel therapeutics to treat human diseases associated with pain and inflammation. Cara possesses both near-term clinical development opportunities combined with proprietary approaches to developing first-in-class novel therapeutics. Cara's most advanced patented compound, CR845, is currently undergoing clinical testing for acute pain. This compound possesses analgesic and anti-inflammatory activities appropriate for multiple therapeutic applications. In addition, Cara aims to develop a future pipeline of first-in-class molecules at novel analgesic and anti-inflammatory targets using its proprietary drug screening technology. Intellectual property:
CR845 was discovered by CARA's scientists. CARA owns six U.S. patents pertaining to CR845 with claims covering compositions of matter and methods of use for CR845. The earliest U.S. patent claiming CR845 compositions will expire no earlier than November 12, 2027. To date CARA has built an extensive patent portfolio with 58 patents issued and 72 pending. Pipeline and Technologies:
CR845 has completed three Phase 2 clinical trials in acute post-operative pain. Cara's most advanced CB compound, CR701, is in preclinical development. CB Antagonists:
Studies on the effects of cannabis have led to the discovery of an endogenous system of ligands involved in pain and inflammation. The main naturally occurring ligands for this system, anandamide and 2-arachidonoylglycerol (2-AG), activate a number of cannabinoid receptors, including CB1 and CB2 receptors. Like opioid receptors, CB1 and CB2 receptors are members of the G
protein-coupled receptor superfamily. CB1 receptors and associated ligands are mainly localized in the brain whereas CB2 receptors are found mainly in peripheral tissues, particularly immune cells such as leukocytes and mast cells, which have been shown to be involved in pain and inflammatory responses. Cara is developing lead molecules that selectively modulate peripheral CB receptors without targeting CNS cannabinoid receptors. Peripheral CB receptor modulators will be initially developed as a novel therapeutic approach for neuropathic pain, a condition currently without consistently effective therapies. Revenue from License Agreements:
All of CARA's revenue to date has been from license agreements. They have received aggregate payments of $28.8 million pursuant to license agreements related to CR845. In April 2013, CARA entered into a license agreement with Maruishi under which CARA granted Maruishi an exclusive license to develop, manufacture and commercialize drug products containing CR845 in Japan in the acute pain and uremic pruritus fields.
Under the terms of the agreement, CARA received a non-refundable and non-creditable upfront license fee of $15.0 million and is eligible to receive an aggregate of $6 million in clinical development milestones and $4.5 million in regulatory milestones. CARA is also eligible to receive tiered royalties, with percentages ranging from the low double-digits to the low twenties, based on net sales of products containing CR845 in Japan, if any, and share in any sub-license fees. Use of Proceeds:
CARA expects to net $52.9 million from its IPO. Proceeds are allocated as follows: $44 million to conduct its planned Phase 3 clinical trials and other development activities for I.V. CR845 $2.1 million to conduct its planned Phase 1 clinical trial for Oral CR845 $4.6 million to conduct its planned Phase 2a clinical trials and other development activities for Oral CR845; and the remainder for working capital and other general corporate purposes.
PIPELINE & TECHNOLOGIES
A service of the U.S. National Institutes of Health Find Studies:
KAPPA RECEPTOR AGONISTS
Opiate analgesics can act through three different types of opioid receptors, called mu, delta, and kappa. Morphine, the most widely used opiate analgesic, acts primarily via activation of the mu opioid receptor located in the central nervous system (CNS).
This CNS action induces pain relief but is also associated with a wide array of CNS-mediated side effects including sedation, respiratory depression, and abuse liability. As a way to avoid these undesirable CNS effects, there has been an effort to develop opioids which activate peripheral opioid receptors present on sensory nerves, but are also largely excluded from the brain. Such compounds are thought to have the potential to provide pain relief (peripheral opioid analgesia) without producing significant CNS side effects. CR845 belongs to this pharmacological class of compounds; it is a potent peripheral kappa opioid receptor agonist with high selectivity over other opioid receptors.
CR845 has completed three Phase 2 clinical trials in acute post-operative pain.
Cara possesses peripherally-selective molecules that interact with kappa opioid receptors present on peripheral, pain-sensing nerves.
These compounds exhibit potent analgesic and anti-inflammatory properties in animals. Unlike currently marketed opioids, these new compounds do not produce inhibition of intestinal transit (ileus), do not induce life-threatening respiratory depression, nor do they elicit signs of addiction or euphoria in animal models.
The degree of kappa receptor selectivity displayed by CR845 ranks as best-in-class compared to all other previously developed compounds for this therapeutic target. Moreover, CR845 displayed no significant affinity for any other non-opioid known receptors.
CR845 & OTHER KAPPA AGONISTS
Cara has developed two peripheral kappa agonists, CR845 and CR665, which display unmatched peripheral selectivity in animal models when compared to first generation kappa compounds.
Both compounds are intrinsically poor at penetrating the blood-brain barrier which decreases the likelihood of CNS-mediated side effects. The peripheral selectivity of CR665 was evaluated in rodents by comparing the 50% effective dose (i.e., A 50 value) to reduce viscero-somatic pain versus the 50% effective dose to induce a CNS-mediated effect. Pain was measured by the number of writhing movements after administration of an irritant into the abdomen, while the CNS effects were determined by impairment of motor coordination (inability to balance on a rotating horizontal rod). As shown (figure), previously developed kappa agonists such as enadoline, asimadoline, and TRK-820 inhibited the pain response at doses only 2- to 8-fold less than those producing an impairment of motor coordination in rodents. CR665, in contrast, showed a much larger safety margin with greater than 500-fold separation of doses required to produce analgesia versus CNS side effect.
Studies on the effects of cannabis (marijuana) have led to the recent discovery of an endogenous system of ligands in humans involved in a number of physiological processes including pain and inflammation.
The main naturally occurring ligands for this system, anandamide and 2-arachidonoylglycerol (2-AG), activate a number of cannabinoid receptors, including CB1 and CB2 receptors. Like opioid receptors, CB1 and CB2 receptors are members of the G protein-coupled receptor superfamily. CB1 receptors and associated ligands are mainly localized in the brain whereas CB2 receptors are found mainly in peripheral tissues, particularly immune cells such as leukocytes and mast cells, which have been shown to be involved in pain and inflammatory responses. Cara is developing lead molecules that selectively modulate peripheral CB receptors without targeting CNS cannabinoid receptors. Peripheral CB receptor modulators will be initially developed as a novel therapeutic approach for neuropathic pain, a condition currently without consistently effective therapies.
Cara's most advanced CB compound, CR701, is in preclinical development.
CR701 has been evaluated in a rodent model of neuropathic pain that produces both hyperalgesia (sensitization of nerve endings to painful stimuli) and allodynia (painful perception of innocuous stimuli) comparable to human conditions. As shown in the figure below, administration of CR701 to animals with neuropathy resulted in significant reversal of both hyperalgesia and allodynia, as measured by responses to thermal and tactile stimuli, respectively.
The most successful and therapeutically useful drug targets in modern medicine are a superfamily of membrane proteins, the G protein-coupled receptors (GPCRs).
This is particularly evident within the pain markets where all of today's clinically effective opioid analgesics and a number of anti-inflammatory agents, such as the leukotriene antagonists, act through this class of receptor protein.
In recent years, studies have demonstrated that GPCRs can form paired protein complexes - dimers - with other GPCRs on the cell surface. Two of the same GPCRs can pair up to form a homodimer , or two different GPCRs can pair up to form a heterodimer. Compared to the GPCR monomers, some of these receptor dimers display new, unexpected drug recognition and response properties, which means that there exists a broad, new array of unexplored drug targets within the GPCR superfamily.
DimerScreen™, is designed to specifically and selectively identify molecules interacting with GPCR dimers and thus allows for the discovery of compounds with new pharmacological properties at identified dimeric drug targets.
Upcoming Projected Clinical Milestones 2016 Reinitiate CLIN3001 Abdominal Pain Trial Q2, 2016
Initiation Uremic Pruritus Phase 2/3 Program Q2, 2016
Initiation 2nd Phase 3 Acute Pain Trial 2H, 2016
Initiation Phase 2b Oral OA Trial 2H, 2016
Novel Peripheral Kappa Opioid Product Candidates: Efficacy Without Opioid Side Effects
Consensus Ratings for Cara Therapeutics (NASDAQ:CARA)
|Ratings Breakdown: ||6 Buy Rating(s) |
|Consensus Rating: ||Buy (Score: 3.00) |
|Consensus Price Target: ||$23.83 (265.54% upside) |
Analysts' Ratings History for Cara Therapeutics (NASDAQ:CARA)
(Data available from 4/29/2014 forward)
|Date ||Firm ||Action ||Rating ||Price Target || |
|4/23/2016 ||Piper Jaffray ||Reiterated Rating ||Overweight ||$23.00 || |
|4/21/2016 ||Needham & Company LLC ||Reiterated Rating ||Buy || || |
|4/20/2016 ||Cantor Fitzgerald ||Reiterated Rating ||Buy || || |
|3/12/2016 ||Janney Montgomery Scott ||Reiterated Rating ||Buy ||$23.00 -> $18.00 || |
|2/29/2016 ||Laidlaw ||Lower Price Target ||Buy ||$30.00 -> $17.00 || |
|11/11/2015 ||Canaccord Genuity ||Reiterated Rating ||Buy ||$30.00 || |
|3/3/2015 ||MLV & Co. ||Initiated Coverage ||Buy ||$26.00 || |
|12/9/2014 ||Summer Street ||Initiated Coverage ||Buy ||$20.00 || |
http://www.caratherapeutics.com/ Start with investors link.
Cara Therapeutics Inc. (NASDAQ:CARA)
Q1 2016 Results Earnings Conference Call
May 5, 2016 04:30 PM ET seekingalpha.com/article/...rnings-call-transcript?part=single
Cara Therapeutics Is Feeling The Pain; But Not For Long
Jun. 2, 2016 3:15 AM ET http://seekingalpha.com/article/3979324-cara-therapeutics-feeling-pain-long
Post-op pain treatment is ~$9B market; if CR845 pulls even 5% that's approx $450M rev. http://seekingalpha.com/article/3977994-biotech-2-attractive-buyout-targets-7-share