I have two candidates:
One is TWOU, a cloud-based SaaS that allows colleges and universities to deliver online degree programs. They’ve got 49 domestic grad programs at 23 universities (MBA at U of Denver, UC-Davis, and Rice, Berkeley cyber security, UC-Davis MBA, Yale Physician Assistant program, Harvard Business Analytics Program, USC Master of Education in School Counseling; Fordham Masters in Social Work; etc)
Most recent quarter with 35% revenue increase YoY, anticipate 35-40% growth in 2018 … http://investor.2u.com/releasedetail.cfm?ReleaseID=1047591
Secondly, and more long-winded… is spark therapeutics, ticker: ONCE.
while there is much bally-hoo about CRISPR, I have to say, show me the clinical data! Many of these companies frankly have none (I’m looking at you Editas)!
Financially, these companies pose a unique issue- once you treat the patient, they may be cured! Great for patients, not so great for the bottom line, particularly for those of us that like recurring & growing revenue! Ultimately, they will have an initial surge in revenue treating all of the addressable market, then regress back to the incidence rate of XYZ disease amongst the population.
So in order to survive as a gene-editing company, you’ll need to do at least one of the following:
-have a platform for many rare diseases (and either be better, cheaper, or have first mover advantage)
-target more common genetic disease (sickle cell, hemophilia, etc)
Lets talk Spark (taken from a prior NPI post):
They have 3 irons in the fire:
-rare genetic disease of the eyeball
-rare genetic diseases of liver-mediated disease (say, hemophilia)
-neurodegenerative disease (in pre-clinical, so we wont discuss)
For the eyeballs:
In October 2015, we announced positive top-line results from our pivotal Phase 3 clinical trial of voretigene neparvovec, the first successfully completed randomized controlled Phase 3 trial of a gene therapy for genetic disease in the United States. The trial of 31 subjects met with statistical significance its primary endpoint, the bilateral multi-luminance mobility test, or MLMT, change score (p = .001), as well as the first two of three secondary endpoints, specifically full-field light sensitivity threshold testing, or FST, (p < .001) and the assigned first eye MLMT change score (p = .001). Statistical significance was not achieved for the third secondary endpoint, visual acuity (p = .17). To date, we have not observed any product candidate-related serious adverse events and no deleterious immune responses in either the Phase 3 trial or in earlier Phase 1 trials. Based on these positive results, we intend to submit a Biologics License Application, or BLA, for voretigene neparvovec with the U.S. Food and Drug Administration, or FDA, as the first step in executing our global regulatory and commercialization strategy…
The Phase 3 trial demonstrated a statistically significant improvement of vision in subjects that were progressing toward complete blindness. On average, subjects in the intervention group demonstrated an improvement of 1.9 light levels on the MLMT one year post-administration. Specifically, nearly two-thirds of these subjects achieved the maximum improvement measurable on the MLMT. Similarly, on average, these subjects achieved a 100-fold improvement in light sensitivity as measured by FST. Further, visual field in the intervention group nearly doubled versus a slight decrease in the control group. In August 2016, we announced positive one-year follow-up data from the Phase 3 trial on the nine control subjects that crossed over after one year and received voretigene neparvovec. Eight of the nine subjects improved as measured by the MLMT, with all eight responders achieving the maximum improvement measurable. The average improvement among all nine subjects was 2.1 light levels. As measured by FST, eight of the nine crossover subjects improved, with the average improvement of all nine subjects being nearly 200-fold. There was one serious adverse event in one eye among the nine subjects that was determined to be related to the surgical procedure rather than voretigene neparvovec. This subject exhibited foveal thinning and a reduction in visual acuity after the surgical procedure, which did not return to baseline. Voretigene neparvovec continues to demonstrate long-lasting effects as measured by both MLMT and FST. Specifically, a cohort of eight subjects that participated in our second Phase 1 clinical trial, and that would have met the eligibility criteria for the Phase 3 trial, continue to experience durable improvement over four years from time of administration, with observation ongoing. Further, in the continuation of the Phase 3 trial, the original intervention group (n = 20) that received voretigene neparvovec demonstrated sustained benefit two years post-treatment as measured by the bilateral MLMT. The average improvement for these eight subjects of 1.9 light levels seen at year one was maintained at year two. (links here: http://discussion.fool.com/forget-crspr-here39s-gene-therapies-d…)
Remarkable results: 93% Gain in functional vision of Phase 3 participants at 1 year with 72% achieving maximum improvement with no product-related adverse events. 3-year data (n=20) and 4 year data (n=4) from Phase 3 with no statistically significant signs of waning effects. >150 fold improvement in light sensitivity, and visual field measures doubling… for a rare disease without a treatment.
Luxturna (voretigene nearvovec) was just approved by the FDA.
Hemophilia B
-no adverse events reported, no thrombotic events noted, no bleeding events noted. (N of 13)
-durability for hemophilia B now out >1 yr in 5 pts, 1 of which >18 months.
- ten participants went from 111 confirmed bleeds to four over a 58 week period post treatment.
- in 10 participants, the number of factor 9 infusions dropped from 675 in the year before treatment to 10 in the 58 weeks post treatment.
On hemophilia, and why Spark could be a game-changer:
The current standard of care for hemophilia B is either prophylactic or on-demand FIX protein replacement therapy, in which frequent intravenous administrations of recombinant FIX are required to stop or prevent bleeding. Prophylactic therapy for hemophilia B, which has been shown to lead to the best outcomes, is practiced only by some adult patients in the United States due to the significant expense, patient inconvenience, concern about lifetime insurance caps and concern about the risk of blood-borne disease transmission from plasma-derived products. We believe that an average adult patient with severe hemophilia B who treats only in response to bleeds uses, on average, $100,000 of FIX concentrate each year. The cost to treat an average adult patient with severe hemophilia B prophylactically has been estimated to reach up to $300,000 or more each year. A gene therapy treatment could offer patients the benefits of prophylaxis without the need for frequent factor infusion. This treatment is partnered with Pfizer.
Spark has a hemophilia A treatment (there are many more hemophilia A patients than B) - and Spark’s recent drop was likely due to BioMarin reporting positive results. I’m not positive how this pans out. When looking at patient oriented outcomes - number of bleeding episodes, need for infusions, etc - both drugs work well. This may be a race for first mover, and price & insurance company approval may play a role here. Regardless, the hemophilia A market is now a crapshoot, but certainly proof of concept for Spark.
So whats their strategy?
Establish a franchise of gene therapies for IRDs (inherited rare disease). The RPE65 and CHM genes are two of more than 220 genes that have been identified to cause IRDs. We believe our capabilities and know-how will allow us to develop treatments for a number of these genetic conditions. In connection with our development of SPK-CHM for choroideremia and other potential product candidates for additional IRDs, we anticipate utilizing technology similar to that developed in our voretigene neparvovec program while leveraging our clinical experience to optimize the clinical trials to best evaluate the safety and efficacy of the particular product candidate
Basically, they want to plug and play for inherited rare eye disease… and likely for hemophilia / other liver mediated disease… and there’s no shortage of potential genetic diseases to battle:
https://en.wikipedia.org/wiki/List_of_genetic_disorders
expected sales of Luxturna are $400m in 2021, and a possible price tag of >1 million for a one-time dose. I like the plug and play system, but then we run into the problem of, “great we cured all of these cases, now where is our next meal / recurring revenue coming from?”
Let’s compare ONCE to EDIT - editas has no clinical trial results. ONCE has a clinically proven platform with at least a few trials under their belt. ONCE is 2+ years ahead of EDIT. Yet somehow, ONCE is valued at 1.8b and EDIT at 1.1b.
Long TWOU, strongly considering ONCE.