Full Press Release Details
Regarding Forward-Looking Statements
This report contains forward-looking statements within the meaning of Section 27A of the
Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, that are based on our management s beliefs and assumptions and on information currently available to our management. All statements
other than present and historical facts and conditions contained in this report, including statements regarding our future results of operations and financial positions, business strategy, plans and our objectives for future operations, are
forward-looking statements. When used in this report, the words aim, anticipate, assume, believe, contemplate, continue, could, due,
estimate, expect, goal, intend, may, objective, plan, predict, potential, positioned, seek, should,
target, will, would, and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology identify forward-looking
statements. Forward-looking statements include, but are not limited to, statements about:
to the section in our Annual Report on Form 20-F for the year ended December 31, 2015 Item 3.D. Risk Factors for a discussion of important factors that may cause our actual results to differ materially from those expressed or
implied by our forward-looking statements. As a result of these factors, we cannot assure you that the forward-looking statements in this report will prove to be accurate. Furthermore, if our forward-looking statements prove to be inaccurate, the
inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation or warranty by us or any
other person that we will achieve our objectives and plans in any specified time frame or at all. We undertake no obligation to publicly update any forward-looking statements, whether as a result
of new information, future events or otherwise, except as required by law.
You should read this report and the documents that we
reference in this report completely and with the understanding that our actual future results may be materially different from what we expect. We qualify all of our forward-looking statements by these cautionary statements.
We are a biopharmaceutical company applying our TransCon technology to develop a pipeline of sustained release prodrug therapies with
best-in-class profiles to address large markets with significant unmet medical needs. We have created a portfolio of potential best-in-class rare disease product candidates to address unmet medical needs by applying TransCon technology to parent
drugs with clinical proof-of-concept. We are developing our most advanced product candidate, TransCon human growth hormone, or TransCon hGH, for once-weekly administration to treat growth hormone deficiency, or GHD, and other indications. In August
2016, we initiated a pivotal global Phase 3 study of TransCon hGH, the heiGHt Trial, in children with GHD. In 2015, we successfully completed a Phase 2 study of TransCon hGH to evaluate the safety and efficacy of once-weekly TransCon hGH in 53
treatment-na ve, pre-pubertal children with GHD.
We are also using our TransCon technology platform to develop TransCon Parathyroid
Hormone, or TransCon PTH, for hypoparathyroidism, a rare endocrine disorder of calcium and phosphate metabolism. We are currently conducting toxicology studies to enable an Investigational New Drug Application, or IND, and expect to file an IND for
TransCon PTH in the second quarter of 2017. We believe our TransCon PTH may solve significant unmet medical needs, and provide patients suffering from hypoparathyroidism with a more physiological parathyroid hormone replacement therapy than
currently approved drugs.
We are also developing TransCon C-Type Natriuretic Peptide, or TransCon CNP, for the treatment of
achondroplasia, the most common form of dwarfism. Currently there are no therapies for achondroplasia approved by the U.S. Food and Drug Administration, or FDA. TransCon CNP is based on our TransCon technology platform and C-type natriuretic
peptide, or CNP, a therapeutic target with extensive preclinical data. We are currently expanding our manufacturing capabilities to support IND-enabling toxicology studies, and we expect to file an IND in the fourth quarter of 2017.
TransCon hGH is being developed for growth hormone deficiency, or GHD, and other indications. GHD is a serious orphan disease that affects
both children and adults. Children with GHD are characterized by short stature, metabolic abnormalities, cognitive deficiencies and poor quality of life. GHD in adults is associated with premature mortality, increased adiposity, or fat mass, as well
as psychiatric-cognitive, cardiovascular, muscular, metabolic and skeletal abnormalities. Human growth hormone, or hGH, is used for the long-term treatment of children and adults that fail to secrete adequate amounts of endogenous growth hormone.
Since the 1990s, the pharmaceutical industry has employed various approaches to develop long-acting growth hormone products to reduce the patient burden of daily injections and increase patient compliance with the dosing regimen. To date, regulatory
authorities have approved only two long-acting growth hormone products, each of which utilize unmodified growth hormone as the active drug substance. Neither of these products has achieved commercial success, due to manufacturing, regulatory,
efficacy, safety and/or tolerability reasons associated with the sustained release technology.
TransCon hGH is a prodrug that releases
unmodified growth hormone and thus maintains the same mode of action as currently prescribed daily hGH therapies, which we believe reduces clinical and regulatory risk. TransCon prodrugs predictably release unmodified active parent drugs and may
offer advantages that include superior efficacy, safety, tolerability and compliance, including less frequent dosing and the ability to switch patients to subcutaneous injections from burdensome continuous infusions.
Using our TransCon technology, we have established a new paradigm that combines the benefits of conventional prodrug and sustained release
technologies, and is broadly applicable to proteins, peptides and small molecules. This has enabled us to create a pipeline of potential best-in-class product opportunities within rare endocrine disorders.
TransCon PTH is being developed for hypoparathyroidism, a rare endocrine disorder of calcium and phosphate metabolism. TransCon PTH is
designed as a once-daily formulation of parathyroid hormone, or PTH(1-34) to maintain a steady concentration of PTH in the blood stream within the normal range, at levels similar to those observed in healthy individuals. TransCon PTH is designed to
address the fundamental limitation of daily injections of short acting PTH molecules, such as Natpara, or PTH(1-84), and Forteo, or PTH(1-34), by providing infusion-like blood levels of PTH. Preclinical experiments in primates have demonstrated that
TransCon PTH has a half-life of
approximately 20 hours. This half-life would be a substantial increase compared to PTH(1-34) and PTH(1-84), both of which after intravenous administration to humans have half-lives of only a few
minutes. We believe this substantial half-life extension of PTH would reflect more closely the physiological levels of PTH observed in healthy individuals, and maintain blood calcium levels and normalize urinary calcium excretion, an improvement
over what is currently feasible with existing approved therapies.
TransCon CNP is being developed for the treatment of achondroplasia,
the most common form of dwarfism. There are currently no FDA-approved pharmacological treatments for achondroplasia, and patients often face multiple surgeries to alleviate its many complications. Administration of CNP to patients with
achondroplasia and in animal models of achondroplasia, has been demonstrated to stimulate growth. Clinical proof-of-principle was recently obtained for vosoritide, a once-daily formulation of CNP. TransCon CNP is designed as a once-weekly
formulation of CNP, and to our knowledge is the only sustained-release CNP product in development. TransCon CNP is designed to address the fundamental limitations of daily administration of CNP, and preclinical experiments in primates have
demonstrated that TransCon CNP has a half-life of approximately 75 hours, which is a substantial increase compared to both wild-type CNP and vosoritide, which have half-lives of approximately 2 minutes and 20 minutes, respectively. We believe this
substantial half-life extension of CNP would enable a once-weekly dosing profile that could achieve higher overall CNP exposure levels in the body. Further, this may lead to improved efficacy, while maintaining peak drug exposure at hemodynamically
safe levels, to avoid the hypotension often associated with daily injections of CNP analogues.
Outside rare endocrine disorders, we have
developed a pipeline of sustained release prodrug product candidates, such as TransCon Ranibizumab in the field of ophthalmology, for which we partnered with Genentech, TransCon Peptides for the treatment of diabetes, for which we partnered
with Sanofi, and TransCon Treprostinil, which demonstrated promising pharmacokinetics in a Phase 1 study in healthy adult volunteers completed in 2015.
We believe that our TransCon technology has been validated by the continued clinical development of our Phase 3 product candidate, TransCon
hGH, and the ongoing development of other rare disease product candidates, as well as by our multi-product collaborations with Sanofi and Genentech.
As of June 30, 2016, we have received approximately 74 million of non-dilutive financing from collaboration partners for
up-front technology licensing fees, assignment of certain intellectual property rights and for services rendered. Additionally, we are eligible to receive up to an aggregate of 200 million in development and regulatory milestone payments
for products currently being developed under our collaboration agreements, as well as sales-based milestone payments and royalties on future net sales of products. We hold worldwide rights to our TransCon technology and have no third-party royalty
or milestone payment obligations with respect to our TransCon technology or any of our product candidates. All of our TransCon prodrugs are new molecular entities and should therefore be eligible to be granted new intellectual property rights,
including new composition of matter patents.
Our Rare Endocrine Disease Product Candidates
TransCon Human Growth Hormone
lead product candidate is TransCon hGH for the treatment of GHD. According to Medtrack, global sales from currently marketed hGH products exceeded $3 billion in 2015. The current standard of care for the treatment of GHD requires patients to receive
daily injections over many years and this administrative burden of daily injections often results in poor patient compliance, potentially leading to suboptimal treatment outcomes. To address these unmet medical needs, we are developing TransCon hGH
for once-weekly administration. Because TransCon hGH is a prodrug that releases unmodified growth hormone, TransCon hGH maintains the same mode of action as currently prescribed daily hGH therapies. Our clinical studies of TransCon hGH have
demonstrated a comparable efficacy, safety, tolerability and immunogenic profile to that of daily growth hormone. If approved, TransCon hGH may reduce the burden of daily treatment by requiring significantly fewer injections, which may improve
patient compliance and treatment outcomes.
We have successfully completed Phase 2 studies of TransCon hGH in children and adults with GHD.
In 2015, we successfully completed a Phase 2 study of TransCon hGH to evaluate the safety and efficacy of once-weekly TransCon hGH in 53 treatment-na ve, pre-pubertal children with GHD. In this Phase 2 trial, mean annualized height velocities
among the three dosing levels administered weekly ranged from 11.9 cm for the 0.14 mg/kg/week dose to 13.9 cm for the 0.30 mg/kg/week dose, which were comparable to 11.6 cm for the active comparator, daily injections of Genotropin at a 0.21 mg/kg/week dose.
In August 2016, we announced the initiation of the
global Phase 3 TransCon hGH heiGHt Trial in children with GHD. The heiGHt trial is a randomized, open-label, active-controlled Phase 3 registration study that is designed to enroll approximately 150 children with GHD who have not previously been
treated. The study is designed with simplified inclusion criteria to facilitate enrollment with a 0.24 mg/kg/week dose, which we believe is within the range acceptable worldwide. The inclusion criteria require pre-pubertal children, bone age that is
at least six months less than chronological age, impaired height that is greater than or equal to two standard deviations, or SD, below predicted, GHD diagnosis confirmed by two different growth hormone stimulation tests and insulin-like growth
factor-1 that is greater than or equal to one SD below predicted. Patients will receive either once-weekly TransCon hGH (0.24 mg/kg/week) or daily injections of Genotropin at 34
g/kg/day (0.24 mg/kg/week) with a 2:1 randomization in a non-inferiority design. The primary endpoint of the trial is height velocity after twelve months of treatment. Patients completing therapy may then enroll in a planned open-label
extension study. We plan to conduct the trial at approximately 100 sites, including sites in North America, Europe, North Africa, and Oceania (Australia/New Zealand). We expect the first patient to be enrolled in the fourth quarter of 2016 with an
update to be provided on recruitment expected in the first half of 2017. We expect to complete the pivotal portion of the Phase 3 trial in 2019. TransCon hGH is covered by several granted patents with expiration dates ranging from 2024-2030, and
patent protection may extend into 2035, if any patents issue from our pending international applications related to TransCon hGH prodrugs and dosing regimens.
In addition, we are developing a state-of-the-art pen device with Medicom Innovation Partner A/S for administration of TransCon hGH that is
designed to be easy-to-use in the pediatric population and leverages proven technologies. The device has a single low-volume injection for all patients of less than 0.6 mL, requires a small needle that is 31 gauge, four millimeters in length and
comparable to daily hGH, provides for room temperature storage, includes an empty-all design, is expected to last for at least four years and will be enabled for Bluetooth connectivity. We expect to use this device in the open-label extension study
that follows the Phase 3 heiGHt trial. We also plan to launch with this device if and when TransCon hGH is approved. The new device is covered by several pending patent applications, and any patents that may issue from these applications are
expected to expire in 2036.
TransCon PTH is being developed for hypoparathyroidism, a rare endocrine disorder of calcium and phosphate metabolism affecting approximately
77,000 patients in the U.S. Hypoparathyroidism patients suffer from numerous comorbidities, including hypocalcemia and hypercalcemia, hypercalciuria, psychiatric disorders, depression, basal ganglia calcifications, lenticular calcifications and
arterial calcifications. Conventional therapy for hypoparathyroidism involves large doses of vitamin D and oral calcium supplementation, which, although often effective, is associated with marked swings in blood calcium (Ca2+) which may result in
both hypercalcemia and hypocalcemia, excess urinary calcium excretion, and nephrocalcinosis. In 2015, Natpara, PTH(1-84), was approved for once-daily subcutaneous injection as an adjunct to vitamin D and calcium in patients with hypoparathyroidism.
Natpara has not demonstrated an ability to reduce incidences of hypercalcemia (elevated serum calcium levels), hypocalcemia (low serum calcium), or hypercalciuria (elevated urinary calcium) relative to conventional therapy in treated patients.
Teriparatide, PTH(1-34), approved since 2002 for the treatment of osteoporosis, has historically been used for treatment of hypoparathyroidism using multiple daily injections, despite not being approved for this indication. Clinical research of
subjects receiving continuous exposure to PTH(1-34), administered by an infusion pump, has demonstrated simultaneous normalization of blood and urine calcium, as well as normalization of bone turnover.
TransCon PTH is designed as a once-daily formulation of PTH(1-34) to maintain a steady concentration of PTH in the blood stream within the
normal range, at levels similar to those observed in healthy individuals and in patients receiving continuous infusion PTH. TransCon PTH is designed to address the fundamental limitation of daily injections of short-acting PTH molecules, by
providing infusion-like blood levels of PTH. Preclinical experiments in primates have demonstrated that TransCon PTH has a half-life of approximately 20 hours, which
would be a substantial increase compared to PTH(1-34) and PTH(1-84), both of which after intravenous administration to humans have half-lives of only a few minutes. We believe this substantial
half-life extension of PTH would reflect more closely the physiological levels of PTH observed in healthy individuals, maintain normal blood calcium levels, normalize urinary calcium excretion, reduce clinical hypercalcemia, reduce clinical
hypocalcemia, normalize serum phosphate and normalize bone turnover.
We expect to file an IND for TransCon PTH in the second quarter of