Enanta Pharmaceuticals Inc (ENTA)

[vinmantoo]

Not sure why the big drop in ENTA today but it may entice me to buy a bit more.

[DewDiligence]

ENTA_presents_preclinical_data_on_EDP-721—an_oral_ HBV_RNA_destabilizer ENTA aims to make the third drug (with EDP-514 and a nuke) in an all-oral function-cure regimen; the data presentation was delivered at the International Liver Conference sponsored by EASL (European Association for Study of the Liver) going on now:

https://www.enanta.com/investors/news-releases/press-release/2021/Enanta-Pharmaceuticals-Presents-New-Data-for-EDP-721-an-Oral-Hepatitis-B-Virus-RNA-Destabilizer-at-the-European-Association-for-the-Study-of-the-Liver-EASL-International-Liver-Congress/default.aspx

Enanta Pharmaceuticals…today reported new preclinical data for EDP-721, a novel, oral hepatitis B virus (HBV) RNA destabilizer being developed for use in an all-oral combination regimen for HBV.

The data demonstrate potent, selective and pangenotypic inhibition of HBV surface antigen (HBsAg), with up to a 3-log drop in the AAV-HBV mouse model. The research on EDP-721 was presented in a poster titled Discovery and Characterization of EDP-721, a Novel Hepatitis B Virus RNA Destabilizer, during the EASL International Liver Congress 2021.

“The data presented today strongly support the continued development of EDP-721 for use in an all-oral regimen to provide a functional cure for HBV,” said Jay R. Luly, Ph.D., President and Chief Executive Officer of Enanta Pharmaceuticals. “While existing therapies for chronic HBV are moderately effective at suppressing HBV DNA, high levels of HBsAg present a key barrier to enduring viral clearance. These new preclinical data demonstrate that EDP-721 significantly reduced HBsAg production up to 3 logs and exhibited additive to synergistic activity with antivirals that target different mechanisms.”

[New MoA info]: …EDP-721 was shown to be a selective inhibitor of the non-canonical poly(A) polymerases, PAPD5 and PAPD7, host factors critical to the post-transcriptional stabilization of HBV RNA. Inhibition of PAPD5/7 results in potent and pangenotypic reduction in HBsAg production with minimal effects on the host transcriptome in uninfected primary human hepatocytes. Oral administration of EDP-721 demonstrated HBsAg reductions of up to 3 logs following 14 days of once-daily dosing in the AAV-HBV mouse model. EDP-721 was also shown to exhibit synergistic antiviral activity in vitro when combined with nucleos(t)ide reverse transcriptase inhibitors or the HBV core inhibitor EDP-514.

Enanta expects to initiate a Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) study to evaluate the safety and tolerability of EDP-721 in healthy volunteers in mid-2021.

[DewDiligence]

Also, slide #24 in ENTA’s new slide set reveals new MoA and other info about EDP-721, the small-molecule HBV RNA destablizer that ENTA hopes will be the third drug in an all-oral functional cure.

[DewDiligence]

Indeed (eom).

[vinmantoo]

A 3 log decrease for a single drug looks quite impressive to me. It makes me excited to see what happens when combination studies happen.

[DewDiligence]

ENTA new_corporate_slide_set—includes EDP-514 data reported today:

https://s22.q4cdn.com/306858242/files/doc_presentations/2021/06/Enanta-Corporate-Presentation-Final-6.22.21.pdf

[DewDiligence]

ENTA reports_positive_phase-1b_data_for EDP-514 in_viremic_HBV patients:

https://www.enanta.com/investors/news-releases/press-release/2021/Enanta-Pharmaceuticals-Reports-Positive-Data-from-Phase-1b-Study-of-EDP-514-a-Hepatitis-B-Virus-HBV-Core-Inhibitor-in-Viremic-Chronic-HBV-Patients/default.aspx

Enanta Pharmaceuticals…today announced positive data from the first two dose cohorts of its Phase 1b study of EDP-514 in viremic chronic HBV patients who were not being treated with a nucleoside reverse transcriptase inhibitor (NUC). The data demonstrated that EDP-514, Enanta’s novel class II oral HBV core inhibitor, was safe and well-tolerated through 28 days of treatment, displayed pharmacokinetics (PK) supportive of once-daily dosing, and resulted in mean HBV DNA reductions of 2.9 and 3.3 logs at 28 days for the 200 mg and 400 mg cohorts, respectively.

“We are extremely pleased with these promising clinical results for EDP-514, which are comparable to the best antiviral effects reported for any core inhibitor to date and also extend the compound’s excellent safety and tolerability profile,” said Jay R. Luly, Ph.D., President and Chief Executive Officer of Enanta Pharmaceuticals. “In particular, we are encouraged by the rapid and robust declines in HBV DNA, which position EDP-514 to be a key component of a combination regimen for HBV. We believe EDP-514, in combination with a NUC and other mechanisms [i.e. EDP-721, ENTA’s small-molecule RNA destabilizer (#msg-164178077)], could provide a foundation for an all-oral treatment approach to achieve functional cures in patients with chronic HBV infection.

The third dosing cohort from this phase-1b EDP-514 trial (800mg; n=6) is still in progress.

Please see the bottom of #msg-163654846 for related info.

[JK2016]

Great PR just released on HBV 1B program.

[DewDiligence]

ENTA latest slide set (5/6/21):

https://s22.q4cdn.com/306858242/files/doc_presentations/2021/05/25/Enanta-Corporate-Presentation-5.6.21-updated-v2.pdf

The only differences between the 5/6/21 (latest) slide set and the 3/31/21 (previous version) slide set are the financial info from FY2Q21 and the inclusion of the phase-1b data for EDP-514 in nuke-suppressed HBV patients.

[DewDiligence]

This is exactly what Jay Luly predicted would happen when people ceased wearing masks and socially distancing.. RSV is normally dormant during summer, but these are not normal times!

[willyw]

https://www.yahoo.com/news/another-respiratory-illness-spreading-across-191511447.html

The Centers for Disease Control and Prevention is warning about RSV, a cold-like respiratory illness, amid a spike in cases across the southern U.S."
...."Experts said they’ve seen an uptick in positive infections in at least a dozen states, including Florida, Georgia, Mississippi, Texas, Kentucky, North Carolina and South Carolina."

[DewDiligence]

ENTA will unveil preclinical data on its oral HBV RNA destablizer, EDP-721, at EASL:

https://finance.yahoo.com/news/enanta-pharmaceuticals-present-preclinical-data-110000538.html

Please see #msg-163654846 (bottom) for background info.

[DewDiligence]

ENTA’s_enterprise value_at_the_current_share_ price ($48.59) is ~$740M, based on 24.1M fully-diluted shares (#msg-163910230) and pro forma cash of $426.1M (#msg-163910195).

[DewDiligence]

ENTA’s fully-diluted* share count @3/31/21=24.1M—an increase of 0.2M since 12/31/20 (#msg-161707883).

The 24.1M figure above consists of: 20.2M basic shares on the 3/31/21 balance sheet (https://www.sec.gov/ix?doc=/Archives/edgar/data/1177648/000156459021026025/enta-10q_20210331.htm#CONSOLIDATED_BALANCE_SHEETS ); and 3.9M options outstanding at 3/31/21 (whether or not exercisable) (ibid, page 13).

*Non-treasury method.

[DewDiligence]

ENTA’s pro forma cash @3/31/21=$426.1M—a decrease of $15.3M since 12/31/20 (#msg-161707561).

The $426.1.4M figure above consists of: $401.6M of net current assets on the 3/31/21 balance sheet (https://www.sec.gov/ix?doc=/Archives/edgar/data/1177648/000156459021026025/enta-10q_20210331.htm#CONSOLIDATED_BALANCE_SHEETS ); and $24.5M of marketable securities on the 3/31/21 balance sheet designated as long-term (e.g. bonds with a time to maturity greater than one year).

[DewDiligence]

Yes, HBV is now the lead program, for all practical purposes. RSV is ready to roll—as soon as the virus makes a re-appearance, which might not be for another six months or so. NASH has been relegated to an afterthought.

[willyw]

Compact, yes.
Each presentation seems to suggest to me the order of importance.

Lately I've been feeling like HBV is getting top billing.
They (and in the last pitch Q and A) have mentioned EDP 514 antiviral and EDP 721 (RNA destabilizer) AND EASL and a submission on 721. They speak of HBV as if it may be on the threshold of becoming curable; at the least a large step towards that.

I become more and more confident about the RSV program.

The last mentioned was the NASH program, and indeed, the covid was mentioned before it.
That was the sequence and that seemed to me also the areas of opportunity ranked, although that was not expressed.

[DewDiligence]

RBC webcast today was compact and informative:

https://event.on24.com/view/presentation/flash/endedNew.html?eventid=3173662&eventuserid=442649498

It will be available for replay in due course.

[willyw]

https://www.journal-of-hepatology.eu/article/S0168-8278(21)00158-6/fulltext (complete text) (partial text available @ natap https://www.natap.org/

Glecaprevir/pibrentasvir + sofosbuvir + ribavirin offers high cure rate for hepatitis C virus retreatment in real-world settings
(My comment- this only has 6 people in it but the implications on re-treating those with DAA resistance AND cirrhosis is of interest. ~Willy)

We read with interest the recent publication by Dietz et al: “Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy” and would like to present additional data regarding salvage hepatitis C virus (HCV) treatment in this difficult-to-cure patient population.

Patients who fail to achieve sustained virologic response (SVR) with approved direct-acting antiviral (DAA) regimens have limited options for successful retreatment. Usage of a regimen containing an NS3/4A protease inhibitor, NS5A replication complex inhibitor, and NS5B polymerase inhibitor with weight-based ribavirin is appropriate for patients for whom even triple-DAA rescue therapy with sofosbuvir/velpatasvir/voxilaprevir did not achieve cure.
........

Results

Six patients began 16-24 weeks of HCV retreatment with glecaprevir/pibrentasvir, sofosbuvir, and ribavirin between July 2018 and March 2020. All patients achieved SVR. Baseline resistance was present in most patients (5/5 assessed for NS5A and 3/4 for NS3), and all had cirrhosis. No patients were on dialysis or had HIV or hepatitis B virus. No patients experienced serious adverse events or died during treatment. See Table 1 for additional patient details.

(One final comment- with newer more effective treatments the vast multitude of infected can be cured. That small segment that fails can be "rescued" with various therapies. That small group which fails those still has hope for a cure. Add to this people who are cured and become re-infected but have DAA resistant variants are not without options. ~W)

[DewDiligence]

ENTA FY2Q21 CC transcript:

https://www.fool.com/earnings/call-transcripts/2021/05/07/enanta-pharmaceuticals-inc-enta-q2-2021-earnings-c/

[vinmantoo]

These were nuke-suppressed patients, so their viral-load levels for both DNA and RNA were already very low at baseline.

Thanks Dew. I didn't realize that. Makes sense that it would be harder to lower several logs from an already low baseline.

We’ll get a read on the viral-load-reducing efficacy of EDP-514 in the separate trial in viremic patients.

I will look forward to that data.

[DewDiligence]

Is a 1-log decrease going to be sufficient to be a good anti-HBV drug?

These were nuke-suppressed patients, so their viral-load levels for both DNA and RNA were already very low at baseline.

We’ll get a read on the viral-load-reducing efficacy of EDP-514 in the separate trial in viremic patients.

I assume ENTA won't be using EDP-514 as a single drug treatment.

Correct. A three-drug combination is probably going to be necessary for a functional cure. ENTA will eventually test EDP-514 + EDP-721 + nuke, aiming for an all-oral functional cure that no other company is attempting, as far as I know.

I guess we have to see how the 800mg dosage does.

The 400mg and 200mg doses showed good coverage at trough (24-hour) levels, so it’s not clear that 800mg will be better.

[vinmantoo]

Are you asking about EDP-514? The phase-1b data, so far, look fine.

Is a 1 log decrease going to be sufficient to be a good anti-HBV drug? I assume ENTA won't be using EDP-514 as a single drug treatment. I guess we have to see how the 800mg dosage does.

[DewDiligence]

Are you asking about EDP-514? The phase-1b data, so far, look fine.

[JK2016]

Thoughts on the PR and updates ?

[DewDiligence]

ENTA reports HBV data_from_ 200mg_and_400mg_cohorts_of EDP-514 phase-1b:

https://www.enanta.com/investors/news-releases/press-release/2021/Enanta-Pharmaceuticals-Reports-Positive-Data-from-Part-2-of-its-Phase-1b-Study-of-EDP-514-in-Chronic-Hepatitis-B-Virus-Patients-on-Treatment-with-a-Nucleoside-Reverse-Transcriptase-Inhibitor/default.aspx

Enanta Pharmaceuticals…today announced positive data from the first two dose cohorts of Part 2 of its Phase 1b study of EDP-514 in chronic hepatitis B virus (HBV) patients already being treated with a nucleoside reverse transcriptase inhibitor (NUC). The data demonstrated that EDP-514, the Company’s novel class II oral HBV core inhibitor, was safe and well-tolerated, displayed pharmacokinetics (PK) supportive of once-daily dosing, and resulted in a mean reduction in HBV RNA of 1 log.

The 800mg cohort is ongoing. Each of the three dosing cohorts and the placebo control arm has 6 patients. Patients are treated for 28 days.

[DewDiligence]

ENTA FY2Q21 results—royalty_revenue=$20.1M—3/31/21_cash=$400M:

https://www.enanta.com/investors/news-releases/press-release/2021/Enanta-Pharmaceuticals-Reports-Financial-Results-for-its-Fiscal-Second-Quarter-Ended-March-31-2021-with-Webcast-and-Conference-Call-Today-at-430-p.m.-ET/default.aspx

ENTA’s royalty rate from ABBV is tiered, as shown in the table in #msg-142808661. The royalty rate is applied to the 50% Glecaprevir component of Mavyret, a 2-drug combination. The royalty tiers reset at the start of each calendar year (like tax brackets), so ENTA’s royalty rate is highest in the fourth calendar quarter (ENTA’s fiscal* Q1) and is lowest during the first calendar quarter (ENTA’s fiscal* Q2—the quarter just reported).

During calendar 1Q21 (ENTA’s FY2Q21*), ABBV sold $415M of Mavyret. ABBV has issued calendar-2021 guidance for Mavyret sales of $2.0B (#msg-163517997), expecting Mavyret sales to pick up as the COVID pandemic recedes, which will enable more backlogged HCV patients to seek treatment.

ENTA’s 3/31/21 cash balance of $400M was down $5M from 12/31/20 (#msg-161624309).

ENTA previously issued FY2021* guidance for gross operating expenses (including non-cash components such as stock-based compensation): $145-165M for R&D; and $27-33M for G&A. The FY2Q21 numbers ($41.5M for R&D; $8.3M for G&A) were consistent with the prior guidance.

*ENTA’s fiscal year ends on September 30.

[DewDiligence]

ABBV maintained its full-year 2021 Mavyret guidance of $2.0B.

[DewDiligence]

ABBV 1Q21 Mavyret sales=$415M, -14% QoQ:

https://news.abbvie.com/news/press-releases/abbvie-reports-first-quarter-2021-financial-results.htm

The $415M consisted of: $170M US (-23% QoQ); and $245M ex-US (-6%, QoQ).

ABBV’s prior guidance for full-year 2021 Mavyret sales is $2.0B (#msg-161451655). This figure could still be met if patient starts (especially in the US) pick up due to lessening of COVID; however, ABBV may lower the guidance during today’s CC.

[DewDiligence]

ENTA could have a meaningful update on the COVID-19 program in the May-6 earnings release. Unlikely, but possible.

[JK2016]

“Today we announced our plans to report our financial results for our fiscal second quarter ended March 31, 2021, at 4:30 p.m. on May 6, 2021. We will also provide an update on the company’s business, including our research and development pipeline. To listen, please register for the webcast here:  https://lnkd.in/dpWng-A”

[DewDiligence]

The only difference between the 4/1/21 slide set and the 2/8/21 slide set is that the latter shows the phase-2 pediatric RSV trial (RSVPEDSs) started in March, 2021.

[DewDiligence]

New corporate slide set:

https://s22.q4cdn.com/306858242/files/doc_presentations/2021/Enanta-Corporate-Presentation_4.1.21-Final.pdf

[DewDiligence]

Any ideas why we fell off a cliff this week so far?

Two reasons that I’m aware of:

1. XBI, a proxy for small/midcap biotech companies, is down almost 10% this week through today’s close;

2. Yesterday, PFE reported the start of a clinical trial for an oral anti-COVID protease inhibitor, an area where ENTA has been working. It turns out that PFE’s “new” COVID drug is merely a reformulated SARS drug from 2003, but many investors (including me, initially) missed this nuance: (#msg-162747158).

[JK2016]

Any ideas why we fell off a cliff this week so far? Ouch.

[DewDiligence]

All-in-one_nasal-swab_Dx_for_ respiratory_viruses_gets_full_FDA_approval—(not_just_an_EUA):

https://www.prnewswire.com/news-releases/fda-permits-marketing-of-first-sars-cov-2-diagnostic-test-using-traditional-premarket-review-process-301249713.html

Bullish for ENTA for the reason mentioned in #msg-156795547.

BioFire Diagnostics LLC, the company selling this test, is private.

[JK2016]

Interesting read posted on Seeking Alpha today:

https://seekingalpha.com/article/4412162-bottom-fishing-club-enanta-pharmaceuticals

[DewDiligence]

ENTA’s_enterprise value_at_the_current_share_ price ($54.78) is ~$870M, based on 23.9M fully-diluted shares (#msg-161707883) and pro forma cash of $441.4M (#msg-161707561).

[DewDiligence]

ENTA’s fully-diluted* share count @12/31/20=23.9M—an increase of 0.6M since 9/30/20 (#msg-159770202).

The 23.9M figure above consists of: 20.1M basic shares on the 12/31/20 balance sheet (https://www.sec.gov/ix?doc=/Archives/edgar/data/1177648/000156459021004983/enta-10q_20201231.htm#CONSOLIDATED_BALANCE_SHEETS ); and 3.8M options outstanding (whether or not exercisable) (ibid, page 13).

*Non-treasury method.

[DewDiligence]

ENTA’s pro forma cash @12/31/20=$441.4M—a decrease of $3.9M since 9/30/20 (#msg-159770118).

The $441.4M figure above consists of: $422.9M of net current assets on the 12/31/20 balance sheet (https://www.sec.gov/ix?doc=/Archives/edgar/data/1177648/000156459021004983/enta-10q_20201231.htm#CONSOLIDATED_BALANCE_SHEETS ); and $18.5M of marketable securities on the 12/31/20 balance sheet designated as long-term (e.g. bonds with a time to maturity greater than one year).

[DewDiligence]

I concur (eom).

[vinmantoo]

While RVS program is the closest to being an approved product, I am pleased about developments in the anti-HBV program. I am also pleased to hear that ENTA is getting closer to selecting anti-Covid-19 drugs, and that their approach is to attack the virus polymerase and virus protease rather than using an entry inhibitor. I know some expressed disappointment that the pace of development wasn't faster but ENTA has great expertise in antivirals and i is better to take a bit longer to generate a better drug. Both drugs are being designed to be orally administered and the idea is that someone beginning to show symptoms or testing positive would get a prescription and begin taking tablets that they can take everyday for a specified time frame. Still a long way to go but the approach sounds really smart.

[DewDiligence]

ENTA FY1Q21 CC transcript:

https://finance.yahoo.com/m/9d9f7e29-6d00-3518-93e7-d65594b4895d/enanta-pharmaceuticals-inc.html

[DewDiligence]

ENTA new corporate slide set:

https://s22.q4cdn.com/306858242/files/doc_presentations/2021/02/Enanta-Corporate-Presentation-2.8.21-FINAL.pdf

[DewDiligence]

ENTA FY1Q21* results—royalty_revenue=$31.7M—12/31/20_cash=$405M:

https://www.enanta.com/investors/news-releases/press-release/2021/Enanta-Pharmaceuticals-Reports-Financial-Results-for-its-Fiscal-First-Quarter-Ended-December-31-2020-with-Webcast-and-Conference-Call-Today-at-430-p.m.-ET/default.aspx

ENTA’s royalty rate from ABBV is tiered, as shown in the table in #msg-142808661. The royalty rate is applied to the 50% Glecaprevir component of Mavyret, a 2-drug combination. During calendar 4Q20 (ENTA’s FY1Q21), ABBV sold $481M of Mavyret. (ABBV issued full-year 2021 guidance for Mavyret sales of $2.0B.)

ENTA’s 12/31/20 cash balance of $405M was down $14M from 9/30/20 (#msg-159678084).

ENTA previously issued FY2021* guidance for gross operating expenses (including non-cash components): $145-165M for R&D; and $27-33M for G&A. FY1Q21 actual operating expenses ($36.7M for R&D; $7.4M for G&A) were inline with the prior guidance.

*ENTA’s fiscal years end on Sep 30.

[DewDiligence]

ABBV’s 2021 Mavyret guidance=$2.0B—(up from actual $1.83B in 2020).

[DewDiligence]

ABBV 4Q20 Mavyret sales=$481M, +16% QoQ, -23% YoY:

https://news.abbvie.com/news/press-releases/abbvie-reports-full-year-and-fourth-quarter-2020-financial-results.htm

The $481M consisted of: $420M US; $461M ex-US.

Mavyret full-year 2020 sales were $1.83B, slightly below ABBV’s most recent guidance of $1.9B.

[JK2016]

ENTA upgrades to neutral by JP Morgan. Price target $55

[DewDiligence]

ENTA’s CSO exercised and held ~$700K of stock two days ago:

https://www.sec.gov/Archives/edgar/data/1177648/000117764821000008/xslF345X03/edgar.xml

The exercised options did not expire until mid-2022 or later.

[DewDiligence]

ENTA hires head of business development:

https://www.enanta.com/investors/news-releases/press-release/2021/Enanta-Pharmaceuticals-Announces-the-Appointment-of-Brendan-Luu-as-Senior-Vice-President-Business-Development/default.aspx

Enanta Pharmaceuticals…today announced the appointment of Brendan Luu as Senior Vice President, Business Development and member of the company’s senior management team. Mr. Luu brings more than 20 years of diversified business development and sales and marketing experience in the pharmaceutical and technology fields to Enanta, spanning a broad range of therapeutic areas, asset stages and deal structures.

ENTA is openly seeking a partner for its NASH program.