Passed up for acquisition by former partner Retrophin Inc., Censa Pharmaceuticals Inc. has found a new home in rare disease specialist PTC Therapeutics Inc., which has agreed to pay $10 million up front for the opportunity to develop CNSA-001 (sepiapterin), a candidate for orphan metabolic diseases, starting with phenylketonuria (PKU). The proposed transaction also includes up to 850,000 shares of PTC common stock (NASDAQ:PTCT), valued around $40 million, plus additional rewards for achieving development, regulatory and commercial milestones.
Shares of PTC closed at $46.91 on May 7, down $1.31.
PKU, an inherited disorder that increases levels of phenylalanine (Phe) in the blood, can lead to intellectual disabilities and other health problems. Though manageable through dietary restriction and other methods, difficulties in adherence to those methods often necessitate medicine to help control Phe levels in the blood. Doctors often enlist Biomarin Pharmaceutical Inc.'s Kuvan (sapropterin dihydrochloride) or Palynziq (pegvaliase), but both face challenges. Kuvan, for example, is only effective for an estimated 30% to 40% of people with PKU and will face generic challengers as early as October. Palynziq, launched in 2018, requires subcutaneous injection and is only available through a REMS program.
A small phase II study of CNSA-001 suggested it could do better, meeting both primary and secondary endpoints, achieving a statistically significant and, according to Censa, a clinically meaningful reduction in blood Phe levels compared to both baseline and a Kuvan-treated control group. According to PTC, 50% more patients responded to CNSA-001 than Kuvan during the trial's course.
CNSA-001 is an oral formulation of synthetic sepiapterin, a precursor to intracellular tetrahydrobiopterin, which is a critical enzymatic cofactor involved in the metabolism and synthesis of numerous metabolic products. The phase II trial, preceded by work Censa did with Retrophin before the latter decided to pass up further co-development in August 2019, made buying Censa an attractive opportunity for South Plainfield, N.J.-based PTC.
Censa's programs focus on diseases associated with defects in the tetrahydrobiopterin (BH4) biochemical pathways, which can lead to intellectual disability and seizures, as well as disorders of movement, swallowing, thermoregulation and behavioral regulation. Due to the near universal adoption of newborn screening for high plasma phenylalanine, primary BH4 deficiency is typically diagnosed at birth, the Wellesley, Mass.-based company said.
Despite Censa having entertained multiple potential partnerships for CNSA-001, PTC's chief business officer, Eric Pauwels, told BioWorld that, as a pure-play rare disease company with experience developing and commercializing inborn errors of metabolism products globally, it was able to present Censa's team with a compelling offer.
That offer, made possible by Retrophin's August 2019 decision to pass on exercising its option to acquire Censa, could prove rewarding for Censa shareholders. In addition to the up-front payment, the deal includes $217.5 million in development and regulatory milestones for the two most advanced CNSA-001 programs and receipt of a priority review voucher. That figure includes $30 million to be paid to Censa in either cash or PTC common stock for completing the enrollment of a phase III trial for CNSA-001 for PKU, $109 million in development and regulatory milestones for each additional indication of CNSA-001, net sales milestones up to $160 million and a contingent value payment of a percentage of annual net sales ranging from single to low double digits.
PTC's commercial-stage portfolio includes two therapies for the treatment of Duchenne muscular dystrophy: Translarna (ataluren) and Emflaza (deflazacort). Its transaction with Censa, expected to close this quarter, was approved by the boards of both companies.
PKU trial ahead
For now, PTC is preparing for the phase III PKU study that lies ahead, one that PTC CEO Stuart Peltz told BioWorld is likely to include around 150 patients randomized 1-to-1 to either a placebo or three different doses of CNSA-001, provided through a six-week course of treatment. Because the potential trial participants are relatively easily identified and trial sites are well-known, it's "a pretty straightforward trial," he said, suggesting the study could begin sometime in 2021. In addition, PTC would likely seek a year's worth of treatment data with which to build a safety database.
In the U.S., about 16,500 people are living with PKU and approximately 350 babies are born with it each year. That statistic comes from Biomarin, which isn't about to give up its pull in the PKU space easily. The company is already developing BMN-307, a gene therapy candidate for the treatment of PKU comprising an adeno-associated virus 5 vector containing the DNA sequence that codes for phenylalanine hydroxylase. In April, Biomarin said the impact of COVID-19 had created uncertainty about when it will be safe for patients to be dosed in Phearless, its phase I/I study of the candidate. But it estimated that dosing will begin in the second half of this year.
According to Biomarin, clinical candidates for PKU are also under evaluation by Homology Medicines Inc., Nestle Health Science SA, Rubius Therapeutics Inc. and Synlogic Inc. and earlier-stage candidates are being developed by Generation Bio Co., Logicbio Therapeutics Inc., Moderna Therapeutics Inc. and Sangamo Therapeutics Inc.