A constant theme that comes up in and often dominates the leading edge of the biopharma sector is the building of better mousetraps. This is certainly the case for New Jersey-based biopharma developer ContraVir Pharmaceuticals (NASDAQ: CTRV), whose phase 2a clinical antiviral candidate CMX157 (http://dtn.fm/sQXh9) is knocking loudly on the door of Gilead Sciences’ (NASDAQ: GILD) Viread® (TDF, or tenofovir disoproxil fumarate) in chronic hepatitis B virus (HBV).
Coming out of the box strong after notably successful phase 1 safety and efficacy trials, ContraVir was quite proud to recently announce (http://dtn.fm/8NxXL) that the ongoing head-to-head phase 2a (multiple ascending dose) clinical study of its highly potent prodrug of tenofovir (TFV), CMX157, is showing serious potential versus Viread. With data points like a 99 percent reduction in viral load (http://dtn.fm/vtJ59) among patients orally dosed with 25 mg of CMX157, compared to a 300 mg TDF dose, the company is obviously excited about CMX157’s ability to deliver significant viral load reduction safely, at a much lower dose. Delimiting systemic/liver toxicity issues has long been the industry brass ring, and it now looks like that goal is considerably within CTRV’s striking distance.
ContraVir sees CMX157 as the backbone of a rapidly emerging combination therapy approach to HBV, where the liver-targeting capabilities of its prodrug candidate help to reduce impact to other tissue systems. There are a list of significant potential advantages for CMX157 over something like Viread at the point of sale, and ContraVir is bucking hard to not only cure HBV, but slice off an ever larger piece of the global HBV therapeutics market, a market that is on track to do a modest 2.4% CAGR through 2024, when it will reach upwards of $3 billion (http://dtn.fm/Y6Qux). The enhanced bioavailability of CMX157’s novel structure compared to existing indications (which also helps deal with liver damage by reducing the indication’s overall circulatory footprint), is now starting to really come to light through the latest clinical results.
Early on, when the company began touting CMX157’s ability to exploit natural lipid uptake mechanisms, and how this candidate showed in vitro HBV aggression 97 times greater than TFV during its phase 1 days, investors should’ve been paying closer attention. The data from this latest clinical work is consistent with extant data stretching back to preclinical work on CMX157, and with around 786,000 people dying worldwide each year (http://dtn.fm/0dQoF) (mostly due to HBV-related liver disease like cirrhosis and liver cancer) from HBV, ContraVir’s work has become a hot topic. CMX157 has previously been found to be well tolerated at dosages up to 100 mg, so the fact that this stuff is basically doing Viread numbers at 25 mg already spells big things for the ongoing dose escalation work being conducted by CTRV.
CMX157 is just the tip of the proverbial iceberg that is ContraVir’s growing pipeline of candidates, a pipeline which includes an impressive next-gen cyclophilin inhibitor with enhanced potency and selectivity, known as CRV431 (http://dtn.fm/5pmBl). With IND-enabling study work in the offing and a target sometime next year for CRV431 clinical trials, CTRV is really shaping up to be one of the leading alternative HBV therapy developers. CRV431’s ability to attack the life cycle of HBV at numerous points along the arc is a key advantage, and that combination therapy strategy the company keeps pushing really starts to make sense when you take a closer look at the potential advantages of CRV431.
These advantages include a sharp reduction in HBV DNA (in vivo), without toxicity, meaning that liver fibrosis can be hugely downgraded as a complication. Pair that up with a demonstrated ability to actually block entry for HBV into liver cells, and it is little wonder that ContraVir is looking to the horizon for a combination approach with CMX157 as the situation commander, and ancillary indications like best-in-class potency CRV431 on street-sweeper detail. Talk about laying down cover fire: CRV431 is anticipated to be effective against all HBV genotypes, offers broad-spectrum blockage of a large portion of specific HBV protein interaction with host cell cyclophilins, and provides a clearly complementary method of action for CMX157.
In short, the company has both the vision and the technology to deliver on a promise to HBV patients that first became apparent with the emergence of what is now basically a lifetime cure for hepatitis C. The HBV field has been driving hard toward this goal, inspired by what has been done in hepatitis C, and it now appears that New Jersey’s own CTRV could be the one to run this ball into the end zone. Moreover, it was very encouraging to investors to see how the New Jersey Economic Development Authority’s highly competitive Technology Business Tax Certificate Transfer Program (which allows New Jersey-based companies to sell R&D tax credits or net operating losses for up to 80 percent of value), provided $1.8 million in non-dilutive funding (http://dtn.fm/ZiI0h) for CTRV, which has been instrumental for this homegrown biopharma success story to put the pedal to the metal on its HBV pipeline.
Hepatitis B is most prevalent in the regions of sub-Saharan Africa and East Asia, where as much as 10 percent of the population in certain areas is chronically infected. Globally, the number of infected ranges upwards of the CDC/WHO official figure of 240 million, and with as many as 2.2 million chronic hepatitis B cases in the U.S. alone, CTRV’s technology could mean that the company is sitting on a potential goldmine, a goldmine that could provide a beacon of hope for millions.
The broader therapeutics market for liver diseases was around $7.5 billion in 2014, and a recent report published by Grand View Research sees the antiviral segment as the most promising, with 8.9 percent growth anticipated through 2022 (http://dtn.fm/sLM3O). The overall liver disease therapy market is on track to surpass $12 billion during that same interval, with the Asia Pacific region expected to do a CAGR similar to the antiviral segment, running around 8.8 percent. There is a huge external market for CTRV, and the possibilities of pipeline commercialization are indeed tantalizing.
Many investors are already talking about how instrumental the addition of biotech veteran Thomas H. Adams, Ph.D., to the CTRV Board back in September has been with regard to all of this, by the way. After all, this is the guy who founded antisense biotech innovator Genta, as well as Gen-Probe, which was acquired by the same Chugai Pharmaceutical (http://dtn.fm/50p7O) that later ended up in a strategic alliance with biopharma juggernaut Roche (OTC: RHHBY). Even without addressing the company’s pivotal phase 3 trial of its FV-100 indication, engineered to reduce incident rates and severity of shingles (herpes zoster), as well as the severe post-herpetic neuralgia (PHN) pain associated with shingles – CTRV is the kind of near-commercialization contender that many biopharma investors dream of.
The market for FV-100 shows a lot of upside potential, in particular, due to a rapidly accumulating adult population across developed countries. In the U.S., the number of persons 65 years and older is projected to go from just 14.5 percent of the overall population two years ago, to 21.7 percent or more of total population by 2040 (http://dtn.fm/S874v). FV-100 has demonstrated safety and efficacy with clinically meaningful reduction in PHN rates versus GlaxoSmithKline’s (NYSE: GSK) Valtrex® (valacyclovir).
With as much as 10 percent fewer of 350 patients treated with FV-100 requiring some form of narcotics for pain control, this fast-acting, low-dose, once-daily, oral antiviral could really become one of CTRV’s money makers. PHN is the most common/clinically relevant complication with shingles, and FV-100’s pivotal phase 3 trial could spell much needed relief, especially for elderly patients who already have trouble sleeping, or who suffer from other quality of life-diminishing problems associated with shingles.
There is a lot to like about ContraVir, take a closer look by visiting www.Contravir.com