Analyst Conference Summary

biotechnology

conference date: February 24, 2022 @ 8:30 AM Pacific Time
for quarter ending: December 31, 2021 (Q4, fourth quarter 2021)

Forward-looking statements

Overview: Surge on R&D collaboration revenue.

Basic data (GAAP):

Revenue was $440 million, up 231% sequentially from $133 million, and up 52% from $290 million year-earlier.

Net income was $225 million, up sequentially from negative $82 million, and up from negative $356 million year-earlier.

EPS (diluted) was $1.41, up sequentially from negative $0.58, and up from negative $2.54 year-earlier.

Guidance:

Full year 2022 revenue over $575 million. Operating expense $835 to $850 million. Net loss 4275 million. Cash and equivalents at end of year about $1.7 billion.

Conference Highlights:

CEO Brett Monia said "Most recently, we initiated Phase 3 studies with olezarsen in patients with severely high triglycerides and donidalorsen in patients with hereditary angioedema. This expands our Phase 3 pipeline to six medicines addressing eight indications. We also advanced our technology, positioning us to build on our leadership in RNA-targeted therapeutics and add value for our future medicines. We look forward to a steady cadence of catalysts throughout this year, highlighted by eplontersen Phase 3 data in patients with hATTR polyneuropathy planned for mid-year. We expect to file for regulatory approval for eplontersen before year end, assuming positive data. We also expect to make continued advancements to expand and diversify our technology. Based on our anticipated near and mid-term catalysts, we believe we are well positioned to drive increasing value for patients and shareholders."

Donidalorsen (PKK-LRx) Phase 2 data in patients with hereditary angioedema was presented at the ACAAI Annual Meeting the first weekend in November 2022. Phase 3 initiated in Q1 2022. Data expected in 2024.

Spinraza sales by Biogen were $na million. Over 11,000 patients being treated. Spinraza royalty rate resets each year. Biogen plans to initiate the Phase 3b Ascend study evaluating the potential benefit of an investigational higher dose of nusinersen in children, teens and adults with later-onset SMA who were previously treated with Evrysdi (risdiplam).

Waylivra (volanesorsen) is approved in the EU for the treatment of adults with genetically confirmed familial chylomicronemia syndrome (FCS) at high risk for pancreatitis. Commercially available in Germany, Austria, Greece, and France. Approved in Brazil in Q3 2021. Now distributed in Europe by Sobi. Not approved in U.S. Waylivra is under review in Brazil for the treatment of familial partial lipodystrophy (FPL). If approved, it will be the first approved treatment for patients with FPL in Brazil.

Tegsedi (Inotersen) is approved in the EU for polyneuropathy in adults with hATTR (hereditary transthyretin amyloidosis). Now commercial in 15 countries, including Portugal, with additional EU launches planned. Now distributed in Europe by Sobi. Expanding into Canada and Latin America.

Q4 is likely to see an increase in R&D spend. But also higher revenue from partners.

Non-GAAP numbers: net income negative $248 million, up sequentially from negative $48 million, and up from $127 million year-earlier. No non-GAAP EPS given.

Cash ended at $2.12 billion, up sequentially from $1.99 billion. Debt was $1.2 billion in convertible senior notes.

In Q3 2021 started the Phase 3 CORE study of olezarsen (IONIS-APOCIII-LRx) in patients with severe hypertriglyceridemia (sHTG). Data from the Phase 2 study was published in the European Heart Journal.

In Q3 2021 reached full enrollment in the Bayer Phase 2b RE-THINc ESRD study of fesomersen (IONIS-FXI-LRx); data expected in the first half of 2022.

Pelacarsen for Lp(a) driven cardiovascular disease achieved 50% enrollment in Q3 2021, resulting in a $25 million milestone payment from Novartis.

ALS therapies are in Phase 3 studies partnered with Biogen. ION541 advanced into Phase 1/2 development in patients with nearly all forms of ALS. Has multiple preclinical programs in development for ALS. ION464 advanced into Phase 1/2 development in patients with multiple system atrophy.

Tofersen (IONIS-SOD1Rx) Phase 3 study completed dosing for ALS patients with SOD-1 mutation with data reported missed the primary endpoint in Q3 2021, but showed positive trends in secondaries.

Results from the eplontersen Phase 3 study in patients with TTR polyneuropathy are due mid-year 2022

In Q3 2021 showed proof of mechanism, a strong indication of proof of concept and good safety and tolerability in a Phase 2 study and a preliminary open-label extension study of cimdelirsen (IONIS-GHR-LRx) in acromegaly patients.

In Q3 2021 Ionis reached a license agreement with Flamingo Therapeutics for the development and commercialization of oncology programs from the Ionis pipeline. Under the terms of the agreement, Ionis is eligible to receive milestone payments and royalties on future product sales of the STAT3, AR, IRF4 and MALAT1 programs. Flamingo retains full rights to its FLAME platform and all lncRNA programs outside of MALAT1.

Eplontersen is being jointly develped with AstraZeneca for hATTR polyneuropathy. Phase 3 data expected mid-year 2022.

In Q4 2021 licensing ION306 (BIIB115) for SMA, at reduced dosing frequency, resulted in a $60 million milestone from Biogen. Initiated the Phase 1/2 HALOS study of ION582 (BIIB121) in patients with Angelman syndrome, resulting in a $10 million payment from Biogen. Three aditional neurological disease programs advanced by Biogen resulted in $23 million in payments.

The Phase 3 study for the AKCEA-TTR-LRx continued enrollment.

Tominsersen for Huntington's may have a regulatory path forward with younger patients, so Roche plans a new Phase 2 trial.

Ionis continues to develop technologies that allow RNA therapies to almost any part of the body, including inhaled agents.

Ionis has a pipeline of about 45 potential drugs. A growing number are wholly-owned.

GAAP Operating expense was $219 million, consisting of $2 million for cost of goods sold; $179 million for R&D and $38 million for selling, general and administrative. Operating income was $221 million. Other income was $4 million. Income tax benefit $0 million.

Q&A selective summary:

Difference of new SMA drug from Spinraza? BIIB115 uses the same mechanism of Spinraza, the objective is to improve potency and the dosing interval, by using a new backbone chemistry. Preclinical data is strong. Biogen has not given guidance on when it will go to the clinic.

AstraZeneca partnership? We work together well on eplontersen. We hope to gain experience that will help us with Ionis-only launches.

ION449, what is meaningful lowering? We will have an update from the Phase 2 trial at a medical meeting in 1H 2022, then in 2H we will present open lable extension data, showing durability. We believe it is a best-in-class molecult. Differentiation is just lowering LDLC and PCSK9 better.

Hypertension competitive landscape? Expecting robust systolic blood pressure reduction. Anything greater than 5 is good, but with resistant patients 10 mm reduction would be a real winner, would be added on top of other medications.

We believe we have a new molecule that could work in tissues that current methods have an inflamatory effect on. We are planning on moving it into development this year.

We have a potential program in prion disease, which we will talk about more later this year.

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