Milestone Pharmaceuticals: Interesting, But Not Well-Differentiated From Generic Competition

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About: Milestone Pharmaceuticals Inc. (MIST)
by: Avisol Capital Partners
Summary

MIST is a recent IPO specialising in CV drugs.

Its lead drug Etripamil is targeting Paroxysmal supraventricular tachycardia, a pretty decent-sized market.

However, the L-type channel blocker drug is not differentiated enough from competition.

Very few drugs are available for the cardiovascular sector, and even fewer companies actually develop a specialty focus in this area. Milestone Pharmaceuticals (MIST) is one of them. The company has a pipeline focusing on CV diseases, and its lead candidate etripamil is in late stage trial targeting paroxysmal supraventricular tachycardia.

The disease and the science

Paroxysmal supraventricular tachycardia or PSVT is a type of supraventricular tachycardia. That means, electric pulses in the heart’s upper chambers do not work properly, and the heart beats too fast to properly fill in blood. People may often not have symptoms for PSVT. Symptoms, when they occur, may include “palpitations, feeling lightheaded, sweating, shortness of breath, and chest pain.” Paroxysmal means episodic, and these occur and end suddenly, are generally idiopathic.

Etripamil is a calcium channel blocker. Calcium channel blockers are used as optional third line treatment for PSVT. Etripamil is a novel, non-dihydropyridine, L-type calcium channel blocker about which the company says the following:

  • "Short half-life: Etripamil is a short-acting drug with a half-life of approximately 30 minutes, meaning it is quickly metabolized by the body, thereby avoiding long-term side effects that can occur with chronic drug therapy

  • Fast onset: Etripamil is designed to be rapidly absorbed into the bloodstream within minutes, allowing it to act quickly on the desired target (electrical conduction system or coronary blood vessels)

  • Convenient administration: We developed etripamil so that it can be conveniently self-administered by patients via a nasal spray device"

Catalyst

Etripamil has an ongoing phase 3 trial. Phase 3 top-line data due June 30, 2020.

It will initiate two phase 2 trials of the same drug in related disorders - atrial fibrillation and angina, in the coming months. The pipeline looks as follows:

Source

Previous trial data

The drug completed a phase 2 trial called NODE-1 and announced positive results two years ago. This was a double-blind, placebo-controlled, dose-ranging trial of intranasal administration of etripamil for the conversion of induced PSVT. PSVT was induced in 104 patients in an electrophysiology lab. The primary objective of the trial was to demonstrate the superiority of at least one of four intranasal etripamil doses (35, 70, 105, 140mg) over placebo in terminating PSVT within 15 minutes of induction. Data was as follows:

Efficacy: After 15 minutes, PSVT conversion rates were significantly higher in the patients receiving etripamil 70mg (87%; 20/23), 105mg (75%; 15/20) and 140mg (95%; 20/21) compared to 35 percent (7/20) receiving placebo (p-values less than 0.001, 0.05, 0.001, respectively, compared to placebo). The conversion rate for patients receiving etripamil 35mg was 65% (13/20) (not significant). The median time to PSVT conversion ranged from 1.82 to 3.03 minutes across all four etripamil treatment arms. Secondary objectives of the trial were to establish a dose-related trend and evaluate the safety of etripamil. A plateauing of an efficacy response was seen starting at the 70mg dose, providing guidance for selection of the Phase 3 dose.

Safety: Etripamil had an acceptable safety profile and was well tolerated. The most common adverse event was nasal discomfort and congestion. Some patients experienced a transient drop in blood pressure at the two highest doses of etripamil (105 and 140mg).

As we do see here, this was a very successful trial, meeting the primary endpoint with statistical significance in all dose ranges except the lowest one, and a plateauing of efficacy at the middle range, with a strong jump at the highest dose. However, despite the availability of other L-type CCBs, using placebo in control reduces the value of the trial.

Execution

The company has a market cap of $486M, a cash balance of $88.05M as of the Dec. quarter, and Burn was -$21.05M last year. However, this data isn't much use because the company just IPO-ed, and things may change as the phase 3 trial continues.

Here’s a chart showing recent insider buy/sells:

Source

The molecule is a New Chemical Entity with IP protection until 2036. MIST is a very new IPO, just launched in May 2019.

Competition

Initial treatment for the symptom is often a vagal maneuver like the common Valsalva maneuver. If that doesn’t work, adenosine may be used in people with normal BP. Calcium channel blockers are currently used if adenosine fails.

Source

Milestone claims that its therapy is less invasive, does not need chronic medication, and works as a bridge to ablation therapy, which most people do not like for its invasive nature. Etripamil is a convenient self-administered nasal spray that has a rapid onset action, and a short half-life, so it quickly leaves the body once its work is done.

Other L-type CCBs have been approved in the US for decades; e.g.: verapamil. This is given through the mouth or as an injection. There are minor safety/efficacy differences with etripamil. A placebo-based study does not bring out competitive differences. We record that the upcoming phase 3 trial is also placebo-controlled. This is not to say this will have an effect on approval; but unless the drug is properly differentiated from generics, there will be no pricing power in the market.

About 2.3 per 1,000 people have PSVT. Women are more prone to the disease than men. There are over 2mn patients in the USA. Here’s some data about the market from the company.

Source

In another slide, the company makes some claims about the market potential for Etripamil. However, unless they can differentiate themselves from low cost genetics, we think these figures are a bit too imaginative.

Specifically, the company provides no justification for the claim that their L-type CCB can acquire 50% of the total addressable market. We find this hard to believe, absent clinical differentiation.

Risks

We have discussed the risks in detail here. Firstly, we think the company is quite overvalued compared to other biopharma stocks. Second, we think they should conduct a proper phase 3 trial with competing drugs in the control. The FDA approval isn’t the end of the game but just the start of it. We have no idea what KOLs and prescription-writers will think of this drug, and how it can be priced, given generic drugs like verapamil sells on Walmart (NYSE:WMT) at $9 retail. We haven’t even discussed other drugs like beta blockers and so on, also used for PSVT and related diseases.

Opinion

We really wanted to make this work because CV meds companies are rare, especially specialty ones like MIST. However, at $550mn market cap, near-term IPO and so on, we find this quite highly priced. Moreover, we do not like the lack of differentiation from existing CCB blockers. So, we will wait for more data on the latter, and better numbers on the former.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.