PTC Therapeutics now with a wealthier pipeline

Before we sell PTC Therapeutics (PTCT), after the stock had reached and surpassed our latest and highest 2018 target, the firm did the right thing that we expected was good enough to encourage investment in this firm.  The good thing is acquiring Agilis Biotherapeutics – a small firm that succeeded in creating innovative gene therapy programs for rare genetic disorders that affect the central nervous system (CNS).

After expressing its excitement about the successful completion of Agilis Biotherapeutics’ acquisition, PTC Therapeutics’ Chief Executive Officer Stuart W. Peltz, Ph.D. described the acquired firm’s scientists as a team with exceptional gene therapy experience, having targeted micro-delivery gene therapy platform, which demonstrated durable clinical benefit, as well as gene therapy manufacturing and R&D capabilities. He expressed his conviction that the acquisition would deepen PTC Therapeutics’ pipeline and, as a combined organization, they will be able to optimally treat a larger number of rare disorders, in addition to accelerating the process of bringing important new therapies to the patients around the world.

What PTC Therapeutics added to its pipeline comprised the following programs:

GT-AADC: An adeno-associated virus (AAV) gene therapy that treats aromatic L-amino acid decarboxylase (AADC) deficiency – a   rare CNS disorder caused by mutations in the dopa decarboxylase (DDC) gene. The deficiency leads to deficits in the neurotransmitters dopamine, norepinephrine, epinephrine, serotonin and melatonin. In the brain, AADC is responsible for the final step in the synthesis of neurotransmitters dopamine (the precursor of norepinephrine and epinephrine) and serotonin (the precursor of melatonin).

Symptoms of AADC deficiency can vary depending on the type of the underlying genetic mutation, behind nullifying the AADC enzyme function. Severe forms of AADC deficiency can arise from specific DNA mutations.

The symptoms include breathing, feeding, and swallowing problems, frequent hospitalizations, and the need for life-long care. Patients with the severe forms often die in the first decade of life due to profound motor dysfunction, autonomic abnormalities, and secondary complications, such as choking, hypoxia, and pneumonia.

The successful outcome of this gene therapy treatment is extremely important as no treatment options other than palliative care currently exist for many AADC patients. Results from clinical studies demonstrate that GT-AADC – treated subjects have regained their motor function and cognitive scales over multiple years following a single gene therapy treatment.

GT-FA: For the treatment of Friedreich ataxia (FA) – an inherited neuromuscular disorder most commonly caused by a single genetic defect in the FXN gene. The defect leads to reduced production of frataxin, a mitochondrial protein, which is important for cellular metabolism and energy production.

FA results in a physically debilitating, life-shortening condition and is the most common hereditary ataxia, with an estimated 5,000 to 10,000 patients in the US (i.e., one in every 50,000 people).  Both male and female children can inherit the disorder.

Symptoms of FA comprise progressive loss of coordination and muscle strength, which lead to the full-time use of a wheelchair; scoliosis (which often requires surgical intervention); diabetes mellitus; hearing and vision impairment; serious heart conditions; and premature death.

The importance of this treatment resides in the current lack of treatment for FA. The existing management of this syndrome aims at symptom relief. No FDA-approved drugs exist to treat the cause of FA.

GT-AS: For the treatment of Angelman syndrome (AS) – a severe neurological development disorder characterized by profound developmental delays, problems with motor coordination (ataxia), balance, and epilepsy.

Individuals with AS do not develop functional speech, have seizures and sleeping difficulties. Angelman Syndrome is caused by a problem with UBE3a gene and affects all races and both genders equally. It is estimated that there are up to 15,000 people in the US living with AS.

Individuals with Angelman Syndrome tend to have a happy demeanor, characterized by frequent laughing, smiling and excitability. Many individuals with this syndrome are attracted to water and take great pleasure in activities like swimming and bathing.

People living with AS require life-long care, intense therapies to help develop functional skills and improve their quality of life, and close medical supervision involving multiple interventions.

There are currently no approved treatments for AS.

GT-RLN: For cognitive disorders associated with several neurodevelopmental and neurodegenerative disorders

The acquisition also includes gene therapy programs in development.

This pipeline has been added to PTC Therapeutics’ pipeline, which consisted of the following:

Ataluren (Translarna™) for Duchenne muscular dystrophy

PTC596: An orally active small molecule that targets tumor stem cell populations by reducing the function, activity and amount of BMI1.

RG7916:  An investigational oral therapeutic which is in two clinical studies: SUNFISH, a trial in childhood-onset (Type II/III) spinal muscular atrophy (SMA) patients, and FIREFISH, a trial in infant onset (Type I) SMA patients.

SMA is a genetic disorder caused by the mutation or deletion of the survival of motor neuron (SMN1) gene. It affects one in around 10,000 live births and in the most severe forms is associated with a high rate of childhood mortality.

SMA consists of progressive loss of motor neurons, muscle weakness and atrophy. The disorder affects intercostal muscles (chest muscles) with patients often die as a result of respiratory complications.

PTC Therapeutics believes that RG7916 may have the potential to target the underlying cause of the disorder by increasing SMN protein levels in the nervous system, muscles, and other tissues through modification of the splicing of the SMN2 gene to generate more full-length SMN mRNA in SMA patients.

PTC Therapeutics Approved Products

Translarna™ (ataluren) has been approved in the European Union for ambulatory patients aged 5 years and older with Duchenne muscular dystrophy resulting from a nonsense mutation in the dystrophin gene.

EMFLAZA® (deflazacort):  Approved in the US for the treatment of Duchenne muscular dystrophy in patients 5 years of age and older.

Prohost Observations

When PTC Therapeutics and Sarepta Therapeutics (SRPT) were both struggling with their investigational Duchenne muscular dystrophy (DMD) products, our enthusiasm was tilted towards for PTC Therapeutics more than for Sarepta. Our reasons for our choice included the fact that its product Translarna™ was granted conditional approval in Europe at that time for its nonsense DMD gene mutation, while Sarepta was struggling to approve its product eteplirsen to no avail due to the small number of candidates recruited in clinical trial and the fact that the dystrophin created in the muscle with its product eteplirsen was shorter than that in normal people.

When Sarepta was granted approval for is product Exondis 51 (eteplirsen) for Duchenne muscular dystrophy in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping, the firm used the revenues wisely in improving its pipeline. It did it through collaborations with other firms and through conducting more clinical trials for combination treatments. And through improving its manufacturing through the acquisition of a manufacturing facility in Massachusetts.

We believe that PTC Therapeutic has made a wise decision acquiring Agilis Biotherapeutics.  

PTC Therapeutics Stock

Symbol:                                                  PTCT

Current Stock Price:                         $41.61

Market CAP:                                        $1.94 Billion

52-week high and Low:                   $54.95- $14.5

Ironically, instead of rallying on the news, the stock experienced some selling. We believe that the selling is temporary and caused by one of the bizarre laws of thumb, which dictate selling the stocks of companies that spend money for any reason regardless of whether the decision was good or bad. This weird law has originated out of the fact that upgrading or downgrading the firms is still based on the firms’ quarterly incomes.

You know what we mean.

Prohost Forward-Looking: Material presented here is for informational purposes only. Nothing in this article should be taken no more than a personal opinion. It should not be considered a solicitation to purchase or sell securities. Before buying or selling any stock mentioned in this publication you should do your own research and reach your own conclusion. Further, as the contents are opinions they may be wrong. We may have positions in securities mentioned in this article. You should take this into consideration before acting on any advice given here. If this makes you uncomfortable, then you do not have to listen to our thoughts and opinions. The current contents do not take into consideration your individual investment objectives. Also, investing in stocks includes risks. Please

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