Oh my, I really hope this passes the trial and rises.

LTR Pharmaceutical (ASX: LTP)

This is not a report or recommendation. Do whatever you want and do your own research. This is the summary of my research for the Stock LTR Pharma. 

LTR Pharma (LTR) is a Brisbane-based pharmaceutical company that was listed on December 11, 2023, at 20 cents. The company is working on gaining approval and marketing an intranasal formulation of Vardenafil, called Spontan, as a treatment for erectile dysfunction (ED). Vardenafil has previously been approved for the treatment of ED but has lost its exclusivity. As this drug is only changing route and is not novel, the requirements for gaining approval for the new formulation are significantly less stringent.

Upcoming Catalysts: May cause a Rise and increased volume (Trading)

The company’s primary catalyst is the results of the bioequivalence clinical study. The study finished recruiting and dosing on March 25th, and results are anticipated by mid-2024. Upon obtaining the results, the company plans to hold meetings with regulatory authorities for pre-submission and seek approval through the 505(b) pathway with the FDA and the Type F application with the TGA. The company will likely raise capital; however, this could be done before the results are released to reduce the chance of any risk.

Erectile Dysfunction (ED)

Erectile Dysfunction has multiple presentations. These include being able to get an erection sometimes, but not every time you want to have sex. 

Being able to get an erection but not having it last long enough for sex

Being unable to get an erection at any time. 

There are many risk factors for erectile dysfunction 

Diseases 

• Diabetes
• Cardiovascular disease 
• Chronic kidney Disease 
• Cancer
• Hypertension

Medications

• Blood pressure medications
• Antidepressant
• Anticholinergic Drugs 
• Many other medications

Lifestyle 

• Obesity 
• Smoking 
• Alcohol
• Not being Physically Active

Mental Health

Depression

Anxiety 

Prevalence of ED
The prevalence of erectile dysfunction (ED) increases with age in Australia. It is estimated that 23.3% of males suffer from ED between the ages of 30 and 80 and 61% of males aged 45 and above. In the United States, it is estimated that approximately 30 million people aged above 18 suffer from erectile dysfunction, which is approximately 18% of the population.

Of those who are suffering from ED, it is estimated that only one-third seek medical attention to help resolve the issue. There is an increase in the availability of telehealth services tailored to treat erectile dysfunction, which improves access to care and medication prescription.

Total Addressable Market

According to the prospectus, the estimated global Total Addressable Market (TAM) in 2021 is $3.6 billion, projected to RISE to $5.9 billion in 2028, assuming an annual growth rate of 7.1%. The United States is expected to represent around 30% of the global market.

Phosphodiesterase 5 Inhibitors (PDE5i)

An erection is a process involving the relaxation of smooth muscle and blood vessels within the penis. During sexual stimulation, the neurons in the penis release nitrous oxide, activating guanylyl cyclase in the smooth muscle and increasing levels of cGMP which relaxes the smooth muscle and increases blood flow to the penis leading to an erection. cGMP is broken down by PDEs, which reduces the potency of the erection. That is where PDE5 inhibitors come in and block the degradation to cGMP. cGMP is regulated jointly by the rate of synthesis by guanylyl cyclase and by the rate of degradation of cGMP by phosphodiesterase (PDEs).

Image from: https://www.mdpi.com/2227-9059/9/4/432

Currently, there are 5 approved PDE5i

It is estimated that in 2011, Sildenafil, Vardenafil and tadalafil combined 4.2 billion dollars; however, this was before some of the drugs became exclusivity and generic versions became available.

Other Treatments

There are different treatment options other than PDE5i, but I won’t explore them here as they are not first-line treatments for ED. My opinion is that medicine is very slow to evolve, and it will take more than three years for any novel treatment to overtake PDE5i as a first-line treatment.

This is the general guidance for other treatments of ED. 

https://www.racgp.org.au/getattachment/0907ba8d-89ef-43f9-a91e-b5610dee1988/Erectile-dysfunction-when-tablets-don-t-work.aspx

Regulatory Approval
Since Vardenafil is already an approved product with a proven safety profile, this may result in a shortened approval process for Spontan through alternative pathways than the standard New Drug Application (NDA). The company has mentioned that it will first obtain approval from the United States FDA and Australia’s TGA before expanding to other markets.

United States FDA 5052b

Veradinfil is an approved product, so it does not need to go through the traditional NDA application or the 505(b)(1) process. The company can use the 5052B pathway as this only requires a change in the route of administration.  The traditional route requires three phases of trials and various safety studies and data. For the application, the company needs to provide the following information:

• Information on patent claims for the drug or its use
• Marketing exclusivity information
• Bioavailability/bioequivalence study
• Bridging studies for reliance on previous FDA approval; if inadequate, a safety and efficacy study may be required
• Ability to rely on the Agency’s previous findings of safety or efficacy for previous approvals
• Clear identification of the drug
• Identification of the application that the company does not have the right to reference or own

In addition to the clinical data, the FDA will review the Chemistry Manufacturing and Control (CMC) data and compliance with Good Manufacturing Practices (GMP). For more detailed information, the FDA guidance documentation can be found at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/applications-covered-section-505b2.

Australia – Therapeutic Goods Administration 
The company will likely need to submit a Category 1 Type F application, a form used to make changes to the registration of prescription medicines. In this case, Type F refers to a major variation, such as a new route of administration. The application requirements are similar to those of the FDA. However, unlike the FDA, the TGA does not offer a market exclusivity period. Additionally, the company has expressed interest in potentially obtaining early commercialisation of the medication through the Special Access Scheme Category B. This would allow a specialist to prescribe the medicines while awaiting formal approval from the TGA. The TGA will review the clinical and GMP data that is available.

Here is some of the guidance documentation. https://www.tga.gov.au/sites/default/files/2024-01/module-1.2.1-application-form-register-vary-registration-prescription-medicines.pdf

Click to access ctd-module-1.pdf

https://www.tga.gov.au/sites/default/files/ichctdm2efficacy.pdf

Completed Clinical Trials

https://pubmed.ncbi.nlm.nih.gov/32504853/ – Explores the effect of Varandfil on nasal tissue and reports that the drug may reduce nasal spasms. The study reported no significant side effects.

https://pubmed.ncbi.nlm.nih.gov/37147929/ – Pharmacokinetics comparison of vardenafil as administered by an intranasal spray formulation vs a 10-mg oral tablet The most important findings of this study are that the peak time (tmax) is 10 minutes for intranasal (IN) administration versus 58 minutes for oral administration. There was less variability in bioavailability with IN versus oral administration and increased bioavailability with IN. Nasal reactions were observed in 50% of the subjects, but these were less severe after the first exposure.

Bioequivalence Study – PK

This study was a Randomised Open-label single-dose two-treatment crossover study n=18. The study aimed to explore the relative bioequivalence of Intranasal vs. Oral administration of Vardenafil in adult males while fasting. Each participant was dosed with each drug and participated for approximately four weeks. The dose was oral tablet 10mg vs. Nasal Spray 5mg.

Measuring the amount of the drug administered and enters into the bloodstream and the rate at which this will occur. The Trial commenced on the 19th of February, with the first patient dosing occurring on the 19th of March. The final patient was recruited, and dosing was completed on the 25th of March. The readouts are expected mid CY24.

Manufacturing 

Mayne Pharma is an Australian company that manufactures active pharmaceutical ingredients (API). It is listed on the stock exchange and has a market capitalisation of approximately 450 million at the time of writing. The company has over 40 years of experience manufacturing API and other products and is well-versed in GMP guidelines as required in Australia and the US.

APTAR/Nanopharm is a pharmaceutical company based in Wales that specialises in developing intranasal drug delivery. They provide formulations as well as the device used for administration. This device has been used in already approved products, meaning labelling for the device should also be approved. This has been an issue for approval before, particularly with Botanix Pharmaceuticals.

Patents:

The patents are available from the prospectus. Upon reviewing the patents, it appears that the protection is quite weak, and the company may face challenges in the future as another competitor might try to develop a similar PDE5i. However, if the FDA approves Verdanafil, it may be exclusive for three years. 

Other Patents:

EP3612259B1 Additionally, a company called Respira Therapeutics has a patent for Dry Powder Inhalation of Vardenafil for pulmonary hypertension. LTR Pharma has indicated that they may want to pursue this patent. Although I am not a patent expert, so take it with a grain of salt, this patent may impact the future development of this.

EP3641774B1 This patent has been granted for the gummy version of Vardenafil

Board of Directors: I quickly read and reviewed their history. They appear to be credible and experienced. 

Management 

Right now, I am only concerned about the Scientific Advisory Board. Each of the individuals has been involved in many clinical trials and a pioneer in their field. 

Scientific Advisory Board – Summary is copy and pasted from the LTP website. 

Prof Eric Chung

Professor Eric Chung is a consultant urological surgeon at the AndroUrology Centre for Sexual, Urinary and Reproductive Excellence and holds professorial academic appointments at the University of Queensland in Brisbane and Macquarie University Hospital in Sydney. He is the Secretary-General of the Asia Pacific Society of Sexual Medicine (APSSM), Past Chair of the Andrology section within the Urological Society of Australia and New Zealand (USANZ) and Chair of the Scientific Committee at the International Society of Sexual Medicine (ISSM). He has been invited as a speaker and surgeon mentor at many national and international meetings and has authored over 130 peer-reviewed papers and book chapters.   

Prof Russ Chess

Professor Russ Chess-Williams is the Director of the Centre for Urology Research and Professor of Pharmacology at Bond University. His main research interests are the physiology and pharmacology of the lower urinary tract and he was involved in the early pre-clinical studies of tamsulosin, solifenacin and mirabegron.

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