075 – Cyclerion SCRAPS Sickle Cell Disease to Focus on CNS! Hepion Interview Follow Up

Cyclerion effectively fails in their Phase 2 Sickle Cell Disease trial but shows mixed CNS data. I go through the positive aspects of the data and discuss the potential for the company (and my position). In the latter part of the video, I do a follow up to the Hepion interview I did with the CEO, Dr. Robert Foster. I also talk about how I plan to play the stock given the upcoming catalysts.

I also touch on Amgen and their AMG510 Phase 2 data that was released in early Oct/2020.

If you want to help out the show (or join the discord), take a look at my patreon: https://www.patreon.com/breakingbiotech

Follow me on twitter @matthewlepoire Send me an email matthewlepoire@gmail.com http://www.breakingbiotech.com #breakingbiotech

Disclaimer: All opinions expressed by Matt in this podcast are solely his opinions. You should not treat any opinion expressed by Matt in this podcast as a specific inducement to make a particular investment or follow a particular strategy, but only as an expression of his opinion. Matt’s opinions are based upon information he considers reliable, but Matt cannot warrant its completeness or accuracy, and it should not be relied upon as such. Matt is not under any obligation to update or correct any information provided in this podcast. Past performance is not indicative of future results. Matt does not guarantee any specific outcome or profit. You should be aware of the real risk of loss in following any strategy or investment discussed in this podcast. #biotech

 

067 – Intercept Pharma’s Ocaliva Fails to get Approval in NASH while FGFs Compete for Best in Class

After delays in scheduling their advisory committee meeting, the FDA finally sends Intercept Pharma ($ICPT) a Complete Response Letter. In the letter, the FDA says that the benefits of Ocaliva shown via surrogate histopathologic endpoints do not sufficiently outweight the risks to support accelerated approval. Intercept will likely need to collect outcomes data to finally get FDA support but this will add significant time before approval.

Meanwhile, NGM Biotherapeutics ($NGM) and Akero ($AKRO) are two NASH companies commercializing their respective FGF molecules for the treatment of NASH. Akero recently released biopsy data from their Phase 2a study showing a strong effect of Efruxifermin in NASH. I talk about how this might be a good opportunity to take a position in 89 Bio, who has a related FGF21 drug.

If you want to help the show, you can donate here: https://tips.pinecast.com/jar/breaking-biotech You can also open an account at Tastyworks using my referral code: https://start.tastyworks.com/#/login?referralCode=ZWQ77XG2PZ

Follow me on twitter @matthewlepoire

Send me an email matthewlepoire@gmail.com

Disclaimer: All opinions expressed by Matt in this podcast are solely his opinions. You should not treat any opinion expressed by Matt in this podcast as a specific inducement to make a particular investment or follow a particular strategy, but only as an expression of his opinion. Matt’s opinions are based upon information he considers reliable, but Matt cannot warrant its completeness or accuracy, and it should not be relied upon as such. Matt is not under any obligation to update or correct any information provided in this podcast. Past performance is not indicative of future results. Matt does not guarantee any specific outcome or profit. You should be aware of the real risk of loss in following any strategy or investment discussed in this podcast. #biotech

 

043 – Sarepta keeps the gene therapy throne in DMD! ContraVir submits NASH IND!

Hey everybody, hope you’re all doing well! In this video, I talk about Pfizer’s DMD gene therapy update that indicates continued Sarepta hegemony in the space. I also talk about ContraVir and their NASH drug, CRV431.

I must have drank too much coffee before recording because I made more than a couple errors this time around. So, if you’re an audio-only listener and hear something that doesn’t sound right, double check the video version, which corrects the mistakes via captions or has it written properly even though I say it wrong (i.e. I say 3E16 when 3E13 is clearly written on the slide).

Thanks to everyone for listening and do your own due diligence if you are considering investing, this is not a substitute for investment advice.

http://www.breakingbiotech.com
Follow me on twitter @matthewlepoire

 

033 – ICPT Takes the Lead in NASH

In today’s episode, I breakdown the ICPT NASH results, followed up by a quick take on SAGE and the latest buyout rumors.

*this is not investment advice*

Relevant links:
http://ir.interceptpharma.com/news-releases/news-release-details/intercept-announces-positive-topline-results-pivotal-phase-3
https://www.sagerx.com/

http://www.breakingbiotech.com

 

032 – GILD Fails Phase 3 in NASH!

On this episode, I talk about results from the Gilead Phase 3 NASH trial that announced no improvement in patients treated with Selonsertib (ASK1 inhibitor). I also talk about the DBVT BLA resubmission and a hot hot Q319 trading idea on CBIO.

Relevant links:
https://www.gilead.com/news-and-press/press-room/press-releases
https://www.dbv-technologies.com/investor-relations/press-releases/
http://ir.catalystbiosciences.com/news-releases

*this is not investment advice, only my opinion and ideas*

http://www.breakingbiotech.com

#biotech #breakingbiotech #nash

 

030 – JP Morgan and Q1-19 Expectations!

Hey everybody! I’m back with a new video talking about news in January from my favorite biotech companies. There was a lot of interesting things from the JP Morgan Healthcare conference and there is a lot of anticipation for data coming out in Q1-2019.

Here, I blast through some updates on $BMY $ESPR $SGMO $AMRN $SRPT $BIIB. Enjoy!

 

 

Viking Therapeutics and Madrigal Pharma go head-to-head

Viking Therapeutics reports their latest phase 2 data with their candidate thyroid hormone receptor β agonist. I compare both the madrigal and viking drug and discuss their potential in the NASH/NAFLD space.

 

*This is not investment advice*

 

 

Relevant links:

http://ir.vikingtherapeutics.com/2018-09-18-Viking-Therapeutics-Announces-Positive-Top-Line-Results-from-Phase-2-Study-of-VK2809-in-Patients-with-Non-Alcoholic-Fatty-Liver-Disease-NAFLD-and-Elevated-LDL-Cholesterol
https://clinicaltrials.gov/ct2/show/NCT02912260?term=madrigal&rank=4
https://clinicaltrials.gov/ct2/show/NCT02927184?term=viking+therapeutics&rank=1

Click to access Madrigal-Company-Overview-September-2018.FINAL_.20180903.pdf

 

MDGL buyout rumors push stock higher!

– Today I look at Madrigal’s Phase 2 results and talk about competitors in the NASH space.
– I also talk about Tandem and how we can use competitors to compare value
– Follow me on twitter @matthewlepoire

*This is not investment advice. I am not liable for any trading decisions you have made.*

 

Madrigal’s NASH Candidate a Winner

The pathophysiology of NASH involves a number of co-morbidities such as:

  • Obesity
  • Metabolic syndrome
  • Type 2 diabetes
  • Cardiovascular and microvascular dysfunction

Therefore, any ideal drug candidate will, at worst, not aggravate these diseases, and at best, eliminate them along with NASH. In my last post, I ruled out ICPT as a good buy because their drug, OCA, increases patient risk for coronary heart disease and type 2 diabetes. Madrigal Pharmaceuticals and Genfit, on the other hand, have drug candidates that show improvement in NASH-related co-morbidities. In this post, I’m going to focus on Madrigal’s MGL-3196 drug, and a follow-up post will look at Genfit’s Elafibranor.

In December 2017, Madrigal announced their drug, MGL-3196 achieved the primary endpoint in their phase 2 NASH study. The important statistically significant takeaways were:

  1. Decreased liver fat (steatosis)
  2. Decreased LDL-C, triglycerides and lipoprotein a
  3. Decreased liver enzymes

This news doubled the stock, increasing its market cap to ~$1.2 billion and rightfully so.

MGL-3196 is a selective beta-thyroid hormone receptor (βTHR) agonist. When βTHR is activated in the liver, it increases metabolic rate and cholesterol metabolism in rodents and primates (Grover GJ et al. 2003). The phase I study conducted by MDGL showed that MGL-3196 was well-tolerated in humans with potent effects to lower blood LDL-C and triglycerides (Taub R et al. 2013). Animal studies showed that βTHR agonism had insulin sensitizing effects similar to rosiglitazone (very strong insulin sensitizer) along with beneficial effects on liver steatosis and blood cholesterol and triglycerides (Taub R et al. 2009). MDGL presented a poster at the AASLD Liver Meeting in Washington, DC in late 2017, which showed that MGL-3196 had a very profound effect on high-fat diet-fed mice, including a variety of beneficial gene expression changes, and normalization of hyperinsulinemia (MDGL press releases, October, 2017).

The final data of their phase 2 study is expected in April, 2018, which will include more formal biopsy data to confirm the MRI techniques they used for the interim analysis.

MGL-3196 and Familial Hypercholesterolemia

MDGL also has a phase 2 trial using MGL-3196 to treat familial hypercholesterolemia (FH, NCT03038022). This disease causes elevated blood cholesterol as a result of a gene mutation and puts patients at an increased risk for atherosclerosis. Heterozygous FH occurs in approximately 1:500 people, and has been traditionally treated by statins (Rader DJ et al. 2003). However, normalizing cholesterol levels in FH patients has proven challenging with the standard of care. If MGL-3196 can show efficacy in FH patients treated with statins, it would provide them another indication and revenue stream.

In 2012, there were about 834 500 American adults with FH (Ferranti SD et al. 2016). The annual cost of nongeneric simvastatin, for example, was $1428 per year (Jick H, et al. 2012). This would generate $1.19 billion for MDGL per year. This estimate is in line with reported revenue of nongeneric statins, such as Zocor, which generated $2.8 billion in sales in 2006 (Merck annual report, 2008), or the combination statin Vytorin (ezetimibe/simvastatin), which generated $1.14 billion in 2016 sales (Merck annual report, 2017).

The data from MDGL’s phase 1 study on LDL-C changes are below (Fig. 1).

Phase I ldl-c data

Figure 1. Adapted from Taub R, et al. 2013. Red box shows effect of MGL-3196 on LDL-C.

At the highest dose, MGL-3196 reduces LDL-C 30% from baseline. This is similar to most market cholesterol lowering drugs according to MDGL’s corporate presentation data (Fig. 2). However, combinations of statins and other drugs are now often prescribed, which are able to reduce LDL-C from baseline by about 50% (Bohula EA, et al. 2015) or 54.2% (Foody M, et al. 2010). Despite these large decreases, LDL-C recommendations of <70mg/dl are only achieved by about 40-60% of patients in these studies. Therefore, MDGL has an opportunity in this arena, but it depends if their drug can be used in combination to significantly lower LDL-C more than what is currently available.

other lipid-lowering

Figure 2. Various drug treatment effects on LDL-C in FH patients.

With all of this in mind, here is my play.

I am going to wait until the phase 2 study data on FH is released before buying anything. Predicting the effectiveness of a combination therapy is very difficult in my experience. If the effect is as strong as already established combination drugs, i.e. Vytorin, it might lead to a ‘sell the news’ event. So I’m going to buy after this data is released, especially if there is a significant drop in the stock. I’m holding out for the end of the NASH phase 3 data, which will not be for 3-5 years. Release of the final NASH phase 2 data will occur around April, 2018, and I will likely pick up more stock then.

In my next post, I’m going to go through Genfit’s Elafibranor, which showed some skeptical phase 2 data in NASH.


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Citations

Grover GJ, Mellström K, Ye L, Malm J, Li YL, Bladh LG, Sleph PG, Smith MA, George R, Vennström B, Mookhtiar K, Horvath R, Speelman J, Egan D and Baxter JD. Selective thyroid hormone receptor-β activation: A strategy for reduction of weight, cholesterol, and lipoprotein (a) with reduced cardiovascular liability. PNAS. 2003.

Taub R, Chiang E, Chabot-Blanchet M, Kelly MJ, Reeves RA, Guertin MC and Tardif JC. Lipid lowering in healthy volunteers treated with multiple doses of MGL-3196, a liver-targeted thyroid hormone receptor-β agonist. Atherosclerosis. 2013.

Taub R, Grimsby J, Laringan JD, Pietranico S, Dvorozniak M and Conde-Knape K. VIA-3196, a Liver-directed Thyroid Beta Agonist for Treating Cardiometabolic Disease. (Abstract) Circulation. 2009.

Rader DJ, Cohen J and Hobbs HH. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J. Clin. Invest. 2003.

Ferranti SD, Rodday AM, Mendelson MM, Wong JB, Leslie LK and Sheldrick RC. Prevalence of Familial Hypercholesterolemia in the 1999 to 2012 United States National Health and Nutrition Examination Surveys (NHANES). Circulation. 2016.

Jick H, Wilson A, Wiggins P and Chamberlin DP. Comparison of prescription drug costs in the United States and the United Kingdom, Part 1: statins. Pharmacotherapy. 2012.

Bohula EA, Giugliano RP, Cannon CP, Zhou J, Murphy SA, White JA, Tershakovec AM, Blazing MA, Braunwald E. Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT. Circulation. 2015.

Foody JM, Brown WV, Zieve F, Adewale AJ, Flaim D, Lowe RS, Jones-Burton C, Tershakovec AM. Safety and efficacy of ezetimibe/simvastatin combination versus atorvastatin alone in adults ≥65 years of age with hypercholesterolemia and with or at moderately high/high risk for coronary heart disease (the VYTELD study). Am J Cardiol. 2010.

 
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