Celsus Therapeutics is a drug development company focusing on novel anti-inflammatory, first-in-class synthetic drugs called multifunctional anti-inflammatory drugs (MFAIDs). Celsus’ proprietary drug technology platform potentially offers an answer to an urgent unmet need: the lack of satisfactory alternatives to corticosteroids in the treatment of a multitude of inflammatory diseases. The company has assembled an experienced team that shares its vision and is committed to making it a success. Dr. Gur Roshwalb joined Celsus as CEO early last year, and DDNews interviewed him about his new company’s progress toward its goals.
DDNews: Dr. Roshwalb, where did Celsus Therapeutics originate and how did it come to be U.S.-based?
Gur Roshwalb: Celsus was spun out from technology developed at Hebrew University in Jerusalem and was incorporated in 2005 in the U.K. Celsus listed in the U.S. in 2013 with new management at the helm and is currently only traded on NASDAQ under the ticker symbol CLTX.
As we advanced, the company required management with drug-development and public-market experience and access to greater institutional capital from well-established healthcare funds. We decided on listing in the U.S. where the biotech/specialty pharma market is active and well-funded. When the board of directors made the decision to go public, new, experienced management with deep healthcare and U.S. public company experience was brought on board.
DDNews: Please describe your “First-in-class multifunctional anti-inflammatory program” and how and why it provides a potential alternative to corticosteroids.
Roshwalb: Celsus’ lead products are first-in-class, novel, nonsteroidal, synthetic anti-inflammatory drugs termed multifunctional anti-inflammatory drugs (MFAIDs) that focus on one of the most sought-after pharmaceutical targets in inflammation research: the sPLA2 family.
This extracellular family of enzymes is a universal early trigger in all of the inflammatory diseases studied that hydrolyze phospholipids on the cell membrane into two key inflammatory precursors: arachidonic acid (AA) and lysophospholipids (LysoPLs).
AA is metabolized via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways to produce large families of eicosanoids; many of them are involved in the development of numerous pathological conditions, especially in inflammation-related processes. These include prostaglandins, thromboxanes and leukotrienes.
LysoPLs induce white cell activation and extravasation, induce cell activation (by lyso phosphatidylserine in particular), induce tissue damage, such as gastric ulceration, and act as growth factors (especially lyso phosphatidic acid) to induce proliferation of cancer cells and tumor metastasis. Furthermore, LysoPLs are also the precursors of platelet activating factor (PAF), possibly the most potent mediator of inflammatory processes.
MFAIDs inhibit sPLA2 with a different chemistry than corticosteroids and are generally specific to inhibiting cell surface sPLA2 activity, thus providing the benefit of inhibition, but, due to the different chemistry, none of the steroid side effects.
DDNews: You have characterized MFAIDS as a potential disruptive technology. How would you define disruptive technology?
Roshwalb: As Clayton Christensen describes, it is a process by which a product or service takes root initially in simple applications at the bottom of a market and then relentlessly moves up market, eventually displacing established products or services.
A good example would be cell phones replacing landlines. For Celsus, it would be our products replacing corticosteroids for inflammation.
DDNews: What is currently happening with each of your four pipeline therapeutics?
Roshwalb: Our most advanced product is MRX-6, a cream formulation currently in Phase 2 development for the treatment of atopic dermatitis (eczema). Our other pipeline products are in preclinical animal testing for inflammation in the eye, lung, joints and bowel.
DDNews: What class of molecule is MRX-6? How are your four current drugs related (or different)?
Roshwalb: MRX-6 is made of a series of sPLA2 inhibitory lipids conjugated to a glycosaminoglycan (hyaluronic acid). The glycosaminoglycan (GAG) is anchored on the cell surface through proteins known as adherins (CD44, as an example), and provide antioxidant benefit, while the lipids conjugated to the GAG act as competitive inhibitors of sPLA2 at the cell surface.
Our pipeline products are similar in that we use various lipids, conjugated in different ways to a set of potential sugars (GAGs).
DDNews: Please describe your expectations for market potential and your patent position for each product.
Roshwalb: The market potential for MRX-6 in skin inflammation is more than $350 million per year in peak U.S. sales, with sales in Europe and Asia bringing in a likely equal amount. Cystic fibrosis and osteoarthritis are both potential multibillion-dollar markets.
We have patent protection on our lead compounds and methods-of-use patents in the United States and major markets around the world, in addition to our pending applications. The other compounds in our pipeline are all new and have long-term composition of matter, formulation and method-of-use potential protection.
DDNews: Finally, what are the reasons you are confident of success when Lilly, Wyeth and Anthera have failed?
Roshwalb: The key to successfully controlling this “universal inflammatory trigger,” or sPLA2, has been demonstrated by the past clinical failures of several pharmaceutical companies. It can be summarized as follows:
1. Inhibit the entire sPLA2 family, not just one or two of its isomers.
2. Do not interfere with the cPLA2 family, a related group of enzymes that are located inside the cell (unlike the sPLA2) and which have a vital homeostatic role (unlike sPLA2) that must not be interfered with.
There are about 12 different isomers of sPLA2, and Lilly’s/Anthera’s compound inhibited the most ubiquitous—subtype IIA. Although they achieved good biomarker results, it is unclear if the compound failed due to an actual lack of benefit or simply because the indications pursued were too difficult (sepsis and post-MI inflammation). The lesson learned is to only pursue indications where we know steroids have demonstrated a benefit.
In Wyeth’s case, the compound inhibited both sPLA2 and cPLA2, which was toxic.
Celsus’ MFAIDs were designed and synthesized to overcome these two critical, and previously insurmountable, problems and represent not just a single molecule but an entire new genus of compounds, each different but with a similar mechanism of action. The glycosaminoglycan backbone is too big to enter the cell, thus not interfering with cPLA2, but very good at anchoring the compound on the target cell surface. The lipids are pan inhibitors of sPLA2.
Gur Roshwalb joined Celsus Therapeutics as CEO in March 2013. From April 2008 to February 2013, he was a vice president at Venrock, where he was an investment professional on the healthcare team investing in both private and public companies. From May 2004 to March 2008, he was a vice president and equity analyst at Piper Jaffray, publishing research on specialty pharmaceutical companies. Prior to Piper, Roshwalb was in private practice in New York and board-certified in internal medicine. He received his M.D. from Albert Einstein College of Medicine and his MBA from the New York University Stern School of Business. Roshwalb trained in internal medicine at the Mount Sinai medical center, where he also served as chief resident from 1997 to 1998.